112 results on '"Pandey BN"'
Search Results
2. pH sensitive surfactant-stabilized Fe3O4 magnetic nanocarriers for dual drug delivery
- Author
-
DUTTA, B, SHETAKE, NG, BARICK, BK, BARICK, KC, PANDEY, BN, PRIYADARSINI, KI, and HASSAN, PA
- Subjects
Curcumin ,DOXORUBICIN ,Magnetic ,ANTITUMOR-ACTIVITY ,Fe3O4 ,IRON-OXIDE NANOPARTICLES ,HYPERTHERMIA ,COMBINATION THERAPY ,CO-DELIVERY ,Drug delivery ,BIOMEDICAL APPLICATIONS ,Nanoparticles ,BREAST-CANCER ,IN-VIVO ,THERMAL THERAPY - Abstract
Highly water-dispersible surfactant-stabilized Fe3O4 magnetic nanocarriers (SMNCs) were prepared by self-assembly of anionic surfactant, sodium dodecyl sulphate (SDS) on hydrophobic (oleic acid coated) nanoparticles and their biomedical applications were investigated. These nanocarriers have an average size of about 10 nm and possess tunable surface charge properties. The formation of an organic coating of SDS was evident from infrared spectroscopy, dynamic light scattering, zeta-potential and thermogravi-metric measurements. These nanocarriers were used for loading of both hydrophilic and hydrophobic anticancer agents such as doxorubicin hydrochloride (DOX) and curcumin (CUR), respectively. DOX was conjugated onto the surface of nanocarriers through electrostatic interaction, whereas CUR was encapsulated into the hydrophobic interlayer between oleic acid and SDS. The toxicity and cellular internalization of drug loaded nanocarriers were investigated against WEHI-164 cancer cell line. Specifically, the drug loading, pH sensitive drug release and cellular internalization studies suggested that these nanocarriers are suitable for dual drug delivery. Furthermore, they show good heating ability under AC magnetic field, thus can be used as effective heating source for hyperthermia treatment of cancer. (C) 2017 Elsevier B.V. All rights reserved.
- Published
- 2018
3. PEG mediated shape-selective synthesis of cubic Fe3O4 nanoparticles for cancer therapeutics
- Author
-
DUTTA, B, SHETAKE, NG, GAWALI, SL, BARICK, BK, BARICK, KC, BABU, PD, PANDEY, BN, PRIYADARSINI, KI, and HASSAN, PA
- Subjects
MAGNETIC NANOPARTICLES ,Magnetic ,PACLITAXEL DRUG ,PEGylation ,Fe3O4 ,IRON-OXIDE NANOPARTICLES ,HYPERTHERMIA ,THERAPY ,THERMAL-DECOMPOSITION ,POLYETHYLENE-GLYCOL ,Drug delivery ,BIOMEDICAL APPLICATIONS ,Nanoparticles ,DRUG-DELIVERY ,SURFACE MODIFICATION - Abstract
A facile strategy for shape-selective synthesis of PEGylated Fe3O4 cubic magnetic nanoparticles (PCMN) by thermal decomposition of Fe (III) acetylacetonate was developed and explored their applications in drug delivery and hyperthermia. The structural analysis by XRD and TEM showed the formation of spinel-structured Fe3O4 nanoparticles of good crystallinity. The presence of carboxyl PEG group on the surface of PCMN provides colloidal stability, non-toxicity and protein resistance characteristics to them. These negatively charged PCMN have high electrostatic binding affinity for positively charged anticancer drug, doxorubicin hydrochloride (DOX) and followed pH responsive release behaviour. The in-vitro cytotoxicity studies using normal human fibroblast (NIH 3T3) cells did not show any significant toxicity when cells were treated with PCMN. However, DOX loaded PCMN (PCMN-DOX) exhibit good cellular internalization and substantial toxicity to mouse skin fibrosarcoma (WEHI-164) cells. In addition, the superparamagnetic nature of these particles with optimal magnetization and excellent specific absorption rate (SAR) under external AC magnetic field makes it a valuable system which can be further used as an effective heating agent for hyperthermia treatment of cancer. (C) 2017 Elsevier B.V. All rights reserved.
- Published
- 2018
4. Hyperthermia therapy of cancer: Need for deeper biological insights for improved therapeutic outcome
- Author
-
Pandey, BN, primary and Shetake, NeenaG, additional
- Published
- 2019
- Full Text
- View/download PDF
5. Modification of radiation-induced murine thymic lymphoma incidence by curcumin
- Author
-
Sarma, HD, primary, Dange, PS, additional, Yadav, HD, additional, Kumar, Vimalesh, additional, Bhilwade, HN, additional, and Pandey, BN, additional
- Published
- 2017
- Full Text
- View/download PDF
6. Doxorubicin enhances131I-rituximab induced cell death in Raji cells
- Author
-
Samuel, G, primary, Kumar, C, additional, Pandey, BN, additional, and Venkatesh, M, additional
- Published
- 2015
- Full Text
- View/download PDF
7. Radioprotection by macerated extract of Nigella sativa in normal tissues of fibrosarcoma bearing mice
- Author
-
Jagtap, AartiG, primary, Velho-Pereira, Reelma, additional, Pandey, BN, additional, Kumar, A, additional, and Mishra, KP, additional
- Published
- 2012
- Full Text
- View/download PDF
8. Enhanced thorium decorporation and mitigation of toxicity through combined use of Liv52® and diethylenetriamine pentaacetate.
- Author
-
Ali M, Kumar Das S, Shetake NG, Pandey BN, and Kumar A
- Subjects
- Animals, Mice, Plant Extracts pharmacology, Plant Extracts chemistry, Male, Chelating Agents pharmacology, Chelating Agents chemistry, Spleen drug effects, Spleen metabolism, Thorium toxicity, Pentetic Acid chemistry, Liver drug effects, Liver metabolism
- Abstract
Thorium-232 (Th-232) is a promising fuel for advanced nuclear reactors. However, in case of internal human exposure to Th, there is currently no effective modality for its removal from liver and skeleton or for mitigating its effect. The FDA-approved agent, diethylenetriaminepentaacetate (DTPA), can remove Th and other actinides from blood circulation only. For the first time, a rationally-selected polyherbal hepatoprotective i.e. Liv52® (L52S), was evaluated in-combination with DTPA for its Th decorporation ability in Swiss mice. Inductively-coupled plasma mass spectroscopic analysis showed that oral administration of L52S in conjunction with DTPA significantly decreased Th burden from liver (20 %) and skeleton (33 %) as well as enhanced Th excretion (∼2.5 folds) through urine in comparison to DTPA or L52S alone. The combinatorial therapy was found to be complementary in-action, ameliorating Th-induced tissue damage in liver, spleen, and bone more effectively than monotherapy. Furthermore, markers of liver function (alanine transaminase) and liver inflammation and fibrosis (NF-κB & keratin) further validated the beneficial effect of L52S. The human consumption of L52S for various liver disorders further supports its clinical application for Th decorporation and mitigation of its health effects., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
9. Macrophage-conditioned medium enhances tunneling nanotube formation in breast cancer cells via PKC, Src, NF-κB, and p38 MAPK signaling.
- Author
-
Melwani PK, Balla MMS, Bhamani A, Nandha SR, Checker R, and Pandey BN
- Subjects
- Humans, Culture Media, Conditioned pharmacology, MCF-7 Cells, Female, Doxorubicin pharmacology, Macrophages metabolism, Macrophages drug effects, src-Family Kinases metabolism, Tumor Microenvironment, Nanotubes chemistry, Signal Transduction drug effects, Cell Movement drug effects, MAP Kinase Signaling System drug effects, NF-kappa B metabolism, Breast Neoplasms metabolism, Breast Neoplasms pathology, p38 Mitogen-Activated Protein Kinases metabolism, Protein Kinase C metabolism
- Abstract
Tumor-associated macrophages (TAMs) secrete cytokines, chemokines, and growth factors in the tumor microenvironment (TME) to support cancer progression. Higher TAM infiltration in the breast TME is associated with a poor prognosis. Previous studies have demonstrated the role of macrophages in stimulating long-range intercellular bridges referred to as tunneling nanotubes (TNTs) in cancer cells. Intercellular communication between cancer cells via TNTs promotes cancer growth, invasion, metastasis, and therapy resistance. Given the important role of TNTs and macrophages in cancer, the role of macrophage-induced TNTs in chemotherapy drug doxorubicin resistance is not known. Furthermore, the mechanism of macrophage-mediated TNT formation is elusive. In this study, it is shown that the macrophage-conditioned medium (MΦCM) partially mimicked inflammatory TME, induced an EMT phenotype, and increased migration in MCF-7 breast cancer cells. Additionally, secreted proteins in MΦCM induced TNT formation in MCF-7 cells, which led to increased resistance to doxorubicin. Transcriptomic analysis of MΦCM-treated MCF-7 cells showed enrichment of the NF-κB and focal adhesion pathways, as well as upregulation of genes involved in EMT, extracellular remodeling, and actin cytoskeleton reorganization. Interestingly, inhibitors of PKC, Src, NF-κB, and p38 decreased macrophage-induced TNT formation in MCF-7 cells. These results reveal the novel role of PKC and Src in inducing TNT formation in cancer cells and suggest that inhibition of PKC and Src activity may likely contribute to reduced macrophage-breast cancer cell interaction and the potential therapeutic strategy of cancer., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)
- Published
- 2024
- Full Text
- View/download PDF
10. Thorium Alters Lung Surfactant Protein Expression in Alveolar Epithelial Cells: In Vitro and In Vivo Investigation.
- Author
-
Das SK, Ali M, Shetake NG, Pandey BN, and Kumar A
- Subjects
- Humans, Mice, Animals, A549 Cells, Pulmonary Surfactant-Associated Proteins metabolism, Alveolar Epithelial Cells metabolism, Alveolar Epithelial Cells drug effects, Thorium
- Abstract
Thorium-232 (Th), the most abundant naturally occurring nuclear fuel, has been identified as a sustainable source of energy. In view of its large-scale utilization and human evidence of lung disorders and carcinogenicity, it is imperative to understand the effect of Th exposure on lung cells. The present study investigated the effect of Th-dioxide (1-100 μg/mL, 24-48 h) on expression of surfactant proteins (SPs) (SP-A, SP-B, SP-C, and SP-D, which are essential to maintain lung's surface tension and host-defense) in human lung cells (WI26 and A549), representative of alveolar cell type-I and type-II, respectively. Results demonstrated the inhibitory effect of Th on transcriptional expression of SP-A, SP-B, and SP-C. However, Th promoted the mRNA expression of SP-D in A549 and reduced its expression in WI26. To a significant extent, the effect of Th on SPs was found to be in accordance with their protein levels. Moreover, Th exposure altered the extracellular release of SP-D/A from A549, which remained unaltered in WI26. Our results suggested the differential role of oxidative stress and ATM and HSP90 signaling in Th-induced alterations of SPs. These effects of Th were found to be consistent in lung tissues of mice exposed to Th aerosols, suggesting a potential role of SPs in Th-associated lung disorders.
- Published
- 2024
- Full Text
- View/download PDF
11. Nano-inducer of ferroptosis for targeted chemotherapy of human triple negative breast carcinoma.
- Author
-
Shetake NG, Das SK, Kumar A, and Pandey BN
- Subjects
- Humans, Cell Line, Tumor, Female, Antineoplastic Agents pharmacology, Antineoplastic Agents administration & dosage, Antineoplastic Agents therapeutic use, HMGB1 Protein metabolism, Magnetic Iron Oxide Nanoparticles chemistry, Triple Negative Breast Neoplasms drug therapy, Triple Negative Breast Neoplasms pathology, Triple Negative Breast Neoplasms metabolism, Ferroptosis drug effects, Doxorubicin pharmacology, Doxorubicin administration & dosage, Doxorubicin therapeutic use, Liposomes chemistry
- Abstract
Triple negative breast carcinoma (TNBC) accounts for 15-20 % of all incident breast cancers (BC) and is known to be highly invasive, has fewer treatment options, and tends to have a worse prognosis. However, due to its biological heterogeneity and diverse clinical and epidemiological behaviors, TNBC lacks a tumor-specific targeted therapy. In the present work we have developed a TNBC-specific targeted nano-delivery agent comprising of a cRGD labeled magneto-liposome (T-LMD) co-encapsulated with oleic acid coated iron oxide nanoparticles (MN-OA) and doxorubicin (Dox) in the liposome bilayer and core, respectively. T-LMD was found to show enhanced uptake and induction of ferroptotic cell death in MDA-MB-231, a TNBC model cell line. Additionally, T-LMD induced ferroptosis was found to be accompanied by release of HMGB1, an immunogenic cell death marker, suggesting its immunogenicity for augmenting the activation of anti-tumor immunity in TNBC. The strategic placement of IONPs in the liposome bilayer of T-LMD facilitates the sensitization of MDA-MB-231 cells to undergo ferroptosis; predominantly via the activation of the iron/lipid metabolism pathway, as validated by use of small molecule ferroptosis inhibitor (ferrostatin-1) and iron chelator (deferoxamine). Activation of ferroptotic cell death was also corroborated by ferroptosis specific-ultrastructural alterations in the shape/size of cellular mitochondria and cell ballooning as observed by transmission electron microscopy and bright field imaging, respectively. Thus, our ferroptosis nano-inducer (T-LMD) can efficiently kill TNBC cells via enhanced LPO and ROS generation leading to membrane damage and consequent release of LDH and HMGB1, induce mitochondrial alterations and enhanced DNA double strand breaks. Altogether, our results suggest significant implications of T-LMD for treatment of TNBC., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)
- Published
- 2024
- Full Text
- View/download PDF
12. Mechanistic insights into Thorium-232 induced liver carcinogenesis: The driving role of Wnt/β-catenin signaling pathway.
- Author
-
Yadav R, Das SK, Ali M, Shetake NG, Pandey BN, and Kumar A
- Subjects
- Animals, Mice, Wnt Signaling Pathway genetics, beta Catenin metabolism, Carcinogenesis chemically induced, Carcinoma, Hepatocellular genetics, Liver Neoplasms chemically induced, Liver Neoplasms genetics
- Abstract
Thorium-232 (Th-232), a naturally-occurring radioactive element with high potential of nuclear fuel is now being utilized in advanced nuclear reactors for CO
2 -free energy generation. To achieve all-round capability in Th-fuel cycle for health and environment, understanding the biological effects of Th-232 at cellular and molecular level are extremely important. The present study investigated long-term effects (6 and 12 months) of Th-232 (4, 10 and 20 mg/kg) on gene expression in mice liver (major target organ). Analysis of differentially expressed genes (DEGs, ≥2.0 folds, p < 0.05) showed that with the increase of Th dose (4 to 20 mg/kg), the number of upregulated DEGs increased and the number of downregulated DEGs decreased significantly. A significant number of upregulated DEGs (10 genes in 6 months and 14 genes in 12 months) were found common between 4 and 20 mg/kg. Gene Ontology analysis revealed significant (Padj ~ 10-6 -10-28 ) enrichment of upregulated DEGs for metabolic process, signal transduction, cell death, cell cycle and cell proliferation. KEGG pathway analysis showed DEGs significantly enriched in several cancer-related pathways including hepatocellular carcinoma (HCC). Protein-protein interaction analysis further revealed statistically significant functional interaction (p-value ~10-6-10-10) among the proteins of HCC, which identified β-catenin as one of the most significant signaling nodes in association with myc, an oncogene and p53, a tumor suppressor. Importantly, these results were corroborated by quantitative real time-polymerase chain reaction and western blotting in liver tissues of animals exposed to Th-232. This study insights Wnt/β-catenin signaling network attributable to drive Th-induced liver carcinogenesis, which may have significant implications for management of long-term effects of Th-232., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)- Published
- 2024
- Full Text
- View/download PDF
13. Diagnostic potential of serum HSP90 beta for HNSCC and its therapeutic prognosis after local hyperthermia therapy.
- Author
-
Shetake NG, Kumar A, Huilgol N, and Pandey BN
- Subjects
- Humans, Squamous Cell Carcinoma of Head and Neck therapy, Pilot Projects, Prognosis, Biomarkers, Tumor, Hyperthermia, Induced, Head and Neck Neoplasms therapy
- Abstract
The present pilot study aims to investigate the diagnostic and prognostic efficacy of serum HSP90 beta in Head and Neck Squamous Cell Carcinoma (HNSCC) patients subjected to localized hyperthermia therapy (HT). Serum levels of HSP90 beta were measured by ELISA and its diagnostic and prognostic efficacy was determined by receiver operating characteristic curve (ROC) analysis. HNSCC patients showed significantly (P<0.05) higher serum levels of HSP90 beta (65.6±13.08 ng/ml) compared to Healthy Controls (HC: 23.5±3.8 ng/ml). No significant difference was observed in serum HSP90 beta levels between complete responders (CR) and non-responders (NR) in the chemo-radiation therapy (CRT) cohort. However, in CRT+HT cohort, CR showed significantly (P = 0.02) lower serum HSP90 beta levels at 24 h after HT (25.6±9.04 ng/ml) compared to NR (130.5±34.2 ng/ml). Youden's index values between HNSCC versus HC, CR versus NR (CRT) and CR versus NR (CRT+HT) were found to be 0.47, 0.45 and 0.80, respectively. Thus, alterations in the serum HSP90 beta after HT suggest its potential in prognosis of HT response in HNSCC patients. Elevated levels of HSP90 beta may serve as a promising diagnostic serum bio-marker for HNSCC. However, further validation in larger patient samples is needed for clinical translation of HSP90 beta as diagnostic and prognostic biomarker., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Shetake et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
- Published
- 2023
- Full Text
- View/download PDF
14. Tunneling nanotubes: The intercellular conduits contributing to cancer pathogenesis and its therapy.
- Author
-
Melwani PK and Pandey BN
- Subjects
- Humans, Cell Communication, Calcium Signaling, Actins, Tumor Microenvironment, Neoplasms therapy, Nanotubes
- Abstract
Tunneling nanotubes (TNTs) are intercellular conduits which meet the communication needs of non-adjacent cells situated in the same tissue but at distances up to a few hundred microns. TNTs are unique type of membrane protrusion which contain F-actin and freely hover over substratum in the extracellular space to connect the distant cells. TNTs, known to form through actin remodeling mechanisms, are intercellular bridges that connect cytoplasm of two cells, and facilitate the transfer of organelles, molecules, and pathogens among the cells. In tumor microenvironment, TNTs act as communication channel among cancer, normal, and immune cells to facilitate the transfer of calcium waves, mitochondria, lysosomes, and proteins, which in turn contribute to the survival, metastasis, and chemo-resistance in cancer cells. Recently, TNTs were shown to mediate the transfer of nanoparticles, drugs, and viruses between cells, suggesting that TNTs could be exploited as a potential route for delivery of anti-cancer agents and oncolytic viruses to the target cells. The present review discusses the emerging concepts and role of TNTs in the context of chemo- and radio-resistance with implications in the cancer therapy., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)
- Published
- 2023
- Full Text
- View/download PDF
15. Imaging of bacterial infection: Harnessing positron emission tomography and Cherenkov luminescence imaging with UBI-derived octapeptide.
- Author
-
Mitra JB, Mukherjee A, Kumar A, Chandak A, Rakshit S, Yadav HD, Pandey BN, and Sarma HD
- Subjects
- Animals, Humans, Fluorodeoxyglucose F18, Staphylococcus aureus, Tissue Distribution, Luminescence, Positron-Emission Tomography methods, Chelating Agents, Gallium Radioisotopes chemistry, Staphylococcal Infections diagnostic imaging
- Abstract
Noninvasive imaging techniques for the early detection of infections are in high demand. In this study, we present the development of an infection imaging agent consisting of the antimicrobial peptide fragment UBI (31-38) conjugated to the chelator 1,4,7-triazacyclononane,1-glutaric acid-4,7-acetic acid (NODAGA), which allows for labeling with the positron emitter Ga-68. The preclinical evaluation of [
68 Ga]Ga-NODAGA-UBI (31-38) was conducted to investigate its potential for imaging bacterial infections caused by Staphylococcus aureus. The octapeptide derived from ubiquicidin, UBI (31-38), was synthesized and conjugated with the chelator NODAGA. The conjugate was then radiolabeled with Ga-68. The radiolabeling process and the stability of the radio formulation were confirmed through chromatography. The study included both in vitro evaluations using S. aureus and in vivo evaluations in an animal model of infection and inflammation. Positron emission tomography (PET) and Cherenkov luminescence imaging (CLI) were performed to visualize the targeted localization of the radio formulation at the site of infection. Ex vivo biodistribution studies were carried out to quantify the uptake of the radio formulation in different organs and tissues. Additionally, the uptake of [18 F]Fluorodeoxyglucose ([18 F] FDG) in the animal model was also studied for comparison. The [68 Ga]Ga-NODAGA-UBI (31-38) complex consistently exhibited high radiochemical purity (>90%) after formulation. The complex demonstrated stability in saline, phosphate-buffered saline, and human serum for up to 3 h. Notably, the complex displayed significantly higher uptake in S. aureus, which was inhibited in the presence of unconjugated UBI (29-41) peptide, confirming the specificity of the formulation for bacterial membranes. Bacterial imaging capability was also observed in PET and CLI images. Biodistribution results indicated a substantial target-to-nontarget ratio of approximately 4 at 1 h postinjection of the radio formulation. Conversely, the uptake of [18 F]FDG in the animal model did not allow for the discrimination of infected and inflamed sites. Our studies have demonstrated that [68 Ga]Ga-NODAGA-UBI (31-38) holds promise as a radiotracer for imaging bacterial infections caused by S. aureus., (© 2023 Wiley Periodicals LLC.)- Published
- 2023
- Full Text
- View/download PDF
16. Deoxyglucose-conjugated persistent luminescent nanoparticles for theragnostic application in fibrosarcoma tumor model.
- Author
-
Sharma KS, Melwani PK, Yadav HD, Joshi R, Shetake NG, Dubey AK, Singh BP, Phapale S, Phadnis PP, Vatsa RK, Ningthoujam RS, and Pandey BN
- Abstract
Deoxyglucose conjugated nanoparticles with persistent luminescence have shown theragnostic potential. In this study, deoxyglucose-conjugated nano-particles with persistent luminescence properties were synthesized, and their theragnostic potential was evaluated in fibrosarcoma cancer cells and a tumor model. The uptake of nano-formulation was found to be higher in mouse fibrosarcoma (WEHI-164) cells cultured in a medium without glucose. Nanoparticles showed a higher killing ability for cancer cells compared to normal cells. A significant accumulation of nanoparticles to the tumor site in mice was evident by the increased tumor/normal leg ratio, resulting in a significant decrease in tumor volume and weight. Histopathological studies showed a significant decrease in the number of dividing mitotic cells but a greater number of apoptotic/necrotic cells in nanoparticle-treated tumor tissues, which was correlated with a lower magnitude of Ki-67 expression (a proliferation marker). Consequently, our results showed the potential of our nano-formulation for cancer theragnosis., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)
- Published
- 2023
- Full Text
- View/download PDF
17. The intercellular communications mediating radiation-induced bystander effects and their relevance to environmental, occupational, and therapeutic exposures.
- Author
-
Buonanno M, Gonon G, Pandey BN, and Azzam EI
- Subjects
- Humans, DNA Damage, Cell Communication, Oxidative Stress, Radiation, Ionizing, Bystander Effect radiation effects, Radiation Injuries
- Abstract
Purpose: The assumption that traversal of the cell nucleus by ionizing radiation is a prerequisite to induce genetic damage, or other important biological responses, has been challenged by studies showing that oxidative alterations extend beyond the irradiated cells and occur also in neighboring bystander cells. Cells and tissues outside the radiation field experience significant biochemical and phenotypic changes that are often similar to those observed in the irradiated cells and tissues. With relevance to the assessment of long-term health risks of occupational, environmental and clinical exposures, measurable genetic, epigenetic, and metabolic changes have been also detected in the progeny of bystander cells. How the oxidative damage spreads from the irradiated cells to their neighboring bystander cells has been under intense investigation. Following a brief summary of the trends in radiobiology leading to this paradigm shift in the field, we review key findings of bystander effects induced by low and high doses of various types of radiation that differ in their biophysical characteristics. While notable mechanistic insights continue to emerge, here the focus is on the many means of intercellular communication that mediate these effects, namely junctional channels, secreted molecules and extracellular vesicles, and immune pathways., Conclusions: The insights gained by studying radiation bystander effects are leading to a basic understanding of the intercellular communications that occur under mild and severe oxidative stress in both normal and cancerous tissues. Understanding the mechanisms underlying these communications will likely contribute to reducing the uncertainty of predicting adverse health effects following exposure to low dose/low fluence ionizing radiation, guide novel interventions that mitigate adverse out-of-field effects, and contribute to better outcomes of radiotherapeutic treatments of cancer. In this review, we highlight novel routes of intercellular communication for investigation, and raise the rationale for reconsidering classification of bystander responses, abscopal effects, and expression of genomic instability as non-targeted effects of radiation.
- Published
- 2023
- Full Text
- View/download PDF
18. Theranostic magnetic nanoparticles enhance DNA damage and mitigate doxorubicin-induced cardio-toxicity for effective multi-modal tumor therapy.
- Author
-
Shetake NG, Ali M, Kumar A, Bellare J, and Pandey BN
- Subjects
- Precision Medicine, Drug Delivery Systems methods, Cell Line, Tumor, Doxorubicin pharmacology, Indocyanine Green, Liposomes, DNA Damage, Phototherapy methods, Magnetite Nanoparticles
- Abstract
The chemo-therapeutic efficacy of Doxorubicin (Dox), a potent anti-cancer drug used in the treatment of several solid tumors, is severely compromised by its cardio-toxicity. To overcome this shortcoming and exploit the utmost theranostic potential of nano-formulations, magnetic nanoparticles co-encapsulated with Dox and indocyanine green (ICG) in a liposomal carrier and tagged with cyclic RGD peptide were rationally designed and synthesized. These magneto-liposomes (T-LMD) showed αvβ3-integrin receptor targeting and higher cyto-toxicity in several cancer cell lines (i.e. lung, breast, skin, brain and liver cancer) in combination with or without gamma radiation or magnetic hyperthermia therapy as compared to clinical liposomal nano-formulation of Dox (Lippod™). Mechanism of chemo-radio-sensitization was found to involve activation of JNK mediated pro-apoptotic signaling axis and delayed repair of DNA double strand breaks. Real time imaging of ICG labeled T-LMD suggested ~6-18 fold higher tumor accumulation of T-LMD as compared to off-target organs (kidney, liver, spleen, intestine, lungs and heart) and resulted in its higher combinatorial (chemo-radio-hyperthermia) tumor therapy efficacy as compared to Lippod™. Moreover, T-LMD showed insignificant toxicity to the heart tissue as suggested by serum levels of CK-MB, histo-pathological analysis, anti-oxidant enzyme activities (Catalase and GST) and markers of cardiac fibrosis, suggesting its potential for targeted multi-modal therapy of cancer., Competing Interests: Declaration of competing interest Authors declare no competing interests., (Copyright © 2022 Elsevier B.V. All rights reserved.)
- Published
- 2022
- Full Text
- View/download PDF
19. Role of calcium ion channels and cytoskeletal proteins in Thorium-232 induced toxicity in normal human liver cells (WRL 68) and its validation in swiss mice.
- Author
-
Yadav R, Das SK, Ali M, Pandey BN, and Kumar A
- Subjects
- Animals, Humans, Liver, Mice, Thorium toxicity, Calcium Channels, Cytoskeletal Proteins
- Abstract
Hepatic disorders reported in humans exposed to Thorium-232 (Th-232) rationalizes the present study investigating the toxicological response of normal human liver cells (WRL 68) and its validation in Swiss mice. Cell count analysis of WRL 68 cells-treated with Th-nitrate (1-200 μM) estimated IC50 of ∼24 μM (at 24 h) and 35 μM (at 48 h). Analysis of cell viability (trypan blue assay) showed the IC50 of ∼172 μM. Phase contrast bright-field microscopy revealed Th-induced morphological changes and cell-released microvesicle-like structures in extracellular space. Th-estimation by ICP-MS (Inductively-coupled plasma mass-spectrometry) showed uptake of Th by cells as a function of concentration and incubation time. Employing DTPA as a chelating agent in cell harvesting solution, cell-internalized/strongly-bound Th was estimated to be ∼42% of total incubated Th. Th-uptake studies in the presence of ion-channel specific inhibitors (e.g. nifedipine, thapsigargin) revealed the role of plasma membrane calcium channels and cytoplasmic calcium in modulating the Th-uptake. Transmission electron microscopy of Th-treated cells showed cell-derived extracellular vesicles, alterations in the shape and size of nucleus and mitochondria as well as cytoplasmic inclusions. The order of Th accumulation in various sub-cellular protein fractions was found to be as cytoskeleton (43%) > cytoplasmic (15%) > chromatin (7%) > nuclear (5%) & membrane (5%). Immunofluorescence analysis of WRL 68 cells showed that Th significantly altered the expression of cytoskeleton proteins (F-actin and keratin), which was further validated in liver tissues of Swiss mice administered with Th-232. Findings herein highlight the role of calcium channels and cytoskeleton in Th-induced toxicity. Keywords: Thorium toxicity; Liver cells; Calcium channels; Sub-cellular targets, Cytoskeleton; Swiss Mice., (Copyright © 2021 Elsevier Ltd. All rights reserved.)
- Published
- 2022
- Full Text
- View/download PDF
20. A Nitronaphthalimide Probe for Fluorescence Imaging of Hypoxia in Cancer Cells.
- Author
-
Kumari R, R V, Sunil D, Ningthoujam RS, Pandey BN, Kulkarni SD, Varadavenkatesan T, Venkatachalam G, and V AKN
- Subjects
- Cell Hypoxia, Fluorescent Dyes chemical synthesis, Humans, MCF-7 Cells, Molecular Docking Simulation, Nitroreductases metabolism, Tumor Cells, Cultured, Fluorescent Dyes chemistry, Optical Imaging
- Abstract
The bioreductive enzymes typically upregulated in hypoxic tumor cells can be targeted for developing diagnostic and drug delivery applications. In this study, a new fluorescent probe 4-(6-nitro-1,3-dioxo-1H-benzo[de]isoquinolin-2(3H)-yl)benzaldehyde (NIB) based on a nitronaphthalimide skeleton that could respond to nitroreductase (NTR) overexpressed in hypoxic tumors is designed and its application in imaging tumor hypoxia is demonstrated. The docking studies revealed favourable interactions of NIB with the binding pocket of NTR-Escherichia coli. NIB, which is synthesized through a simple and single step imidation of 4-nitro-1,8-naphthalic anhydride displayed excellent reducible capacity under hypoxic conditions as evidenced from cyclic voltammetry investigations. The fluorescence measurements confirmed the formation of identical products (NIB-red) during chemical as well as NTR-aided enzymatic reduction in the presence of NADH. The potential fluorescence imaging of hypoxia based on NTR-mediated reduction of NIB is confirmed using in-vitro cell culture experiments using human breast cancer (MCF-7) cells, which displayed a significant change in the fluorescence colour and intensity at low NIB concentration within a short incubation period in hypoxic conditions., (© 2021. The Author(s).)
- Published
- 2021
- Full Text
- View/download PDF
21. Mechanism of thorium-nitrate and thorium-dioxide induced cytotoxicity in normal human lung epithelial cells (WI26): Role of oxidative stress, HSPs and DNA damage.
- Author
-
Das SK, Ali M, Shetake NG, Dumpala RMR, Pandey BN, and Kumar A
- Subjects
- Cell Count, DNA Damage, Epithelial Cells, Humans, Lung chemistry, Nitrates toxicity, Oxidative Stress, Reactive Oxygen Species, Thorium analysis, Thorium Dioxide
- Abstract
Inhalation represents the most prevalent route of exposure with Thorium-232 compounds (Th-nitrate/Th-dioxide)/Th-containing dust in real occupational scenario. The present study investigated the mechanism of Th response in normal human alveolar epithelial cells (WI26), exposed to Th-nitrate or colloidal Th-dioxide (1-100 μg/ml, 24-72 h). Assessment in terms of changes in cell morphology, cell proliferation (cell count), plasma membrane integrity (lactate dehydrogenase leakage) and mitochondrial metabolic activity (MTT reduction) showed that Th-dioxide was quantitatively more deleterious than Th-nitrate to WI26 cells. TEM and immunofluorescence analysis suggested that Th-dioxide followed a clathrin/caveolin-mediated endocytosis, however, membrane perforation/non-endocytosis seemed to be the mode of Th internalization in cells exposed to Th-nitrate. Th-estimation by ICP-MS showed significantly higher uptake of Th in cells treated with Th-dioxide than with Th-nitrate at a given concentration. Both Th-dioxide and nitrate were found to increase the level of reactive oxygen species, which seemed to be responsible for lipid peroxidation, alteration in mitochondrial membrane potential and DNA-damage. Amongst HSPs, the protein levels of HSP70 and HSP90 were affected differentially by Th-nitrate/dioxide. Specific inhibitors of ATM (KU55933) or HSP90 (17AAG) were found to increase the Th- cytotoxicity suggesting prosurvival role of these signaling molecules in rescuing the cells from Th-toxicity., (Copyright © 2021 Elsevier Ltd. All rights reserved.)
- Published
- 2021
- Full Text
- View/download PDF
22. Integrated transcriptomic and proteomic analysis of microplasts derived from macrophage-conditioned medium-treated MCF-7 breast cancer cells.
- Author
-
Melwani PK, Balla MMS, S N, Padwal M, Chaurasia RK, Basu B, Ghosh A, and Pandey BN
- Subjects
- Breast Neoplasms genetics, Breast Neoplasms metabolism, Cell Adhesion, Cell Culture Techniques, Cell Line, Tumor, Cell Movement, Chromatography, Liquid, Disease Progression, Female, Gene Expression Regulation, Neoplastic, Gene Regulatory Networks, High-Throughput Nucleotide Sequencing, Humans, MCF-7 Cells, Macrophages chemistry, Protein Interaction Maps, Tandem Mass Spectrometry, U937 Cells, Breast Neoplasms pathology, Culture Media, Conditioned chemistry, Extracellular Vesicles genetics, Extracellular Vesicles metabolism, Gene Expression Profiling methods, Macrophages cytology, Proteomics methods
- Abstract
Microplasts are large extracellular vesicles originating from migratory, invasive, and metastatic cancer cells. Here, to gain insight into the role of microplasts in cancer progression, we performed a proteomic and transcriptomic characterization of microplasts isolated from MCF-7 breast cancer cells treated with macrophage-conditioned medium. These cells were found to be viable, highly migratory, and metabolically active, indicating that microplasts derived from these cells are not apoptotic bodies. Transcriptomic/proteomic analyses identified 10273 mRNAs and 821 proteins in microplasts. Interestingly, 377 microplast mRNAs coded for corresponding microplast proteins. Microplast mRNAs and proteins were mainly associated with binding and catalytic activities. Microplasts showed enrichment of mRNAs involved in transcription regulation and proteins involved in processes such as cell-cell adhesion and translation. Pathway analysis showed enrichment of ribosomes and carbon metabolism. These results suggest a close resemblance between microplasts and parent cells, with mRNA and protein cargo relevant in intercellular signaling., (© 2021 Federation of European Biochemical Societies.)
- Published
- 2021
- Full Text
- View/download PDF
23. Cytoproliferative effect of low dose alpha radiation in human lung cancer cells is associated with connexin 43, caveolin-1, and survivin pathway.
- Author
-
Rajan V and Pandey BN
- Subjects
- Animals, Caveolin 1 analysis, Cell Line, Tumor, Cell Proliferation radiation effects, Connexin 43 analysis, Humans, Lung Neoplasms pathology, Mice, Signal Transduction physiology, Survivin analysis, Alpha Particles therapeutic use, Caveolin 1 physiology, Connexin 43 physiology, Lung Neoplasms radiotherapy, Survivin physiology
- Abstract
Purpose: High LET including alpha radiation-based approaches have been proved as a promising mode for cancer therapy owing to their biophysical and radiobiological advantages compared to photon beams. Studies pertaining to effect of α-radiation on cancer cells are limited to cytotoxic high doses., Materials and Methods: In this study, human lung adenocarcinoma (A549) cells were α-irradiated using
241 Am α-irradiator and effects of low dose of alpha radiation on these cells was studied under in vitro and in vivo conditions., Results: Clonogenic and other assays showed increased cellular proliferation at lower doses (1.36 and 6.8 cGy) but killing at higher doses (13.6-54.4 cGy). Further studies at low dose of alpha (1.36 cGy) showed increased TGF-β1 in the conditioned medium (CM) at early time point (24 h) but CM replacement did not affect the clonogenic survival. In these cells, increased phosphorylation of connexin 43 was correlated with decrease in gap-junction communication observed by dye transfer co-culture experiment. A decrease in caveolin-1 but increase in survivin expression was observed in low dose α-irradiated cells. An increase in cyclinD1 and decrease in Bcl-2, the target proteins of survivin, was observed in these cells. Low dose α-irradiated cancer cells transplanted in SCID mice showed significantly higher tumor volume, which was accompanied with an increased fraction of mitotic and PCNA/Ki67 positive cells in these tumor tissues., Conclusions: Taken together, our results suggest an increase in proliferation and tumor volume at in vitro and in vivo levels, respectively, when A549 cells were irradiated with low dose of α-radiation. These findings may be relevant for a better understanding of radiobiological processes during high LET-based cancer radiotherapy.- Published
- 2021
- Full Text
- View/download PDF
24. Prognosis of metastasis based on age and serum analytes after follow-up of non-metastatic lung cancer patients.
- Author
-
Balla MMS, Patwardhan S, Melwani PK, Purwar P, Kumar A, Pramesh CS, Laskar S, and Pandey BN
- Abstract
At the diagnostic stage, metastasis detection is around 75% in the lung cancer patients. Major clinical challenge faced by medical oncologists is the unpredictable metastasis development in non-metastatic patients. The literature regarding the biomarkers/factors prognosticating metastasis in non-metastatic patients during follow-up is very limited. In this pilot study, the levels of serum biomarkers (IL-8, VEGF, MMP-2, MMP-9) were measured at diagnosis stage of non-metastatic lung cancer patients and these observations were evaluated for metastasis development after follow-up of median 29.2 months. After follow-up, ∼40% of these patients developed metastasis. The average age of non-metastatic patients which later developed metastasis, was found to be lower than the patients continued to be non-metastatic. These patients also showed higher levels of IL-8 and MMP-9 than the patients which did not develop metastasis. Analysis of Receiver Operating Characteristic Curves, Youden's Index and positive likelihood ratio values showed better diagnostic ability for IL-8 and MMP-9, which improved when both markers used together. Moreover, patients with age ≤60 years showed higher prognostic ability of metastasis development, which was significantly enhanced when patient age was analysed with IL-8. These results suggest potential of serum analytes (IL-8, MMP-9) and/or patient age in prognosticating the metastasis development in non-metastatic patients., Competing Interests: Declaration of Competing Interest None, (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2021
- Full Text
- View/download PDF
25. Low-dose radiation therapy for coronavirus disease-2019 pneumonia: Is it time to look beyond apprehensions?
- Author
-
Pandey BN
- Abstract
Coronavirus disease-2019 (COVID-19) has become a global health crisis. Mortality associated with COVID-19 is characterized mainly by acute respiratory distress syndrome (ARDS), sepsis, pneumonia, and respiratory failure. The pathogenesis of the disease is known to be associated with pro-inflammatory processes after virus infection. Hence, various therapeutic strategies are being developed to control the inflammation and cytokine storm in COVID-19 patients. Recently, low-dose radiation therapy (LDRT) has been suggested for the treatment of pneumonia/ADRS in COVID-19 patients through irradiation of lungs by gamma/X-ray. In this direction, a few clinical trials have also been initiated. However, a few recent publications have raised some concerns regarding LDRT, especially about possibilities of activation/aggressiveness of virus (severe acute respiratory syndrome coronavirus 2 in case of COVID-19), lung injury and risk of second cancer after low-dose therapy. The present manuscript is an attempt to analyze these apprehensions based on cited references and other available literature, including some from our laboratory. At this point, LDRT may be not the first line of therapy. However, based on existing anti-inflammatory evidence of LDRT, it needs encouragement as an adjuvant therapy and for more multi-centric clinical trials. In addition, it would be worth combining LDRT with other anti-inflammatory therapies, which would open avenues for multi-modal therapy of pneumonia/ARDS in COVID-19 patients. The mode of irradiation (local lung irradiation or whole-body irradiation) and the window period after infection of the virus, need to be optimized using suitable animal studies for effective clinical outcomes of LDRT. However, considering ample evidence, it is time to look beyond the apprehensions if a low dose of radiation could be exploited for better management of COVID-19 patients., Competing Interests: There are no conflicts of interest., (Copyright: © 2020 Annals of Thoracic Medicine.)
- Published
- 2020
- Full Text
- View/download PDF
26. Glutamic acid-coated Fe 3 O 4 nanoparticles for tumor-targeted imaging and therapeutics.
- Author
-
Dutta B, Nema A, Shetake NG, Gupta J, Barick KC, Lawande MA, Pandey BN, Priyadarsini IK, and Hassan PA
- Subjects
- Cell Survival drug effects, Doxorubicin chemistry, Doxorubicin metabolism, Doxorubicin pharmacology, Drug Carriers chemistry, Humans, Hydrogen-Ion Concentration, MCF-7 Cells, Magnetic Resonance Imaging, Methotrexate chemistry, Methotrexate metabolism, Methotrexate pharmacology, Neoplasms diagnostic imaging, Surface Properties, Contrast Media chemistry, Ferrosoferric Oxide chemistry, Glutamic Acid chemistry, Magnetite Nanoparticles chemistry
- Abstract
We have developed surface functionalised Fe
3 O4 magnetic nanoparticles (MNPs) based system that can be used for tumor-targeted multimodal therapies and MR imaging. Biocompatible, non-essential amino acid (glutamic acid) was introduced onto the surface of Fe3 O4 MNPs to provide functional sites for binding of chemotherapeutic drugs. These glutamic acid-coated Fe3 O4 MNPs (GAMNPs) exhibit good water-dispersibility, magnetic responsivity and pH dependent charge conversal feature. The magnetic core as well as organic shell of GAMNPs was characterized by XRD, TEM, DLS, FTIR, PPMS and UV-visible spectroscopy and zeta-potential analyzer etc. The broad spectrum anticancer drugs, doxorubicin hydrochloride (DOX) and methotrexate (MTX) were electrostatically and covalently conjugated to the surface of GAMNPs, respectively for combination chemotherapy. These dual drugs loaded system (DOX-MTX-GAMNPs) shows pH dependent release behaviour of both the drugs and enhanced toxicity towards breast cancer cell line (MCF-7) as compared to their individual treatment. Fluorescence microscopy and flow cytometric analyses confirmed the successful uptake of drug loaded system into MCF-7 cell lines. Further MTX being analogue of folic acid, its co-delivery with DOX would help in internalization of both the drugs into MCF-7 cells. These GAMNPs also show good heating efficiency under AC magnetic field (Intrinsic loss power, ILP = 0.95 and 0.73 and 0.48 nHm2 /Kg at Fe concentration of 0.5, 1 and 2 mg/ml, respectively) and transverse relaxivity (r2 = 152 mM-1 s-1 ) indicating their potential capability for hyperthermia therapy and MRI tracking. Furthermore, it has been observed that the combination of chemotherapeutic drugs and hyperthermia leads to an enhancement of cytotoxicity in MCF-7 cells., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020. Published by Elsevier B.V.)- Published
- 2020
- Full Text
- View/download PDF
27. Development of surface functionalized hydroxyapatite nanoparticles for enhanced specificity towards tumor cells.
- Author
-
Verma G, Shetake NG, Pandrekar S, Pandey BN, Hassan PA, and Priyadarsini KI
- Subjects
- Animals, Apoptosis drug effects, Cell Line, Tumor cytology, Cell Survival drug effects, Doxorubicin pharmacology, Drug Delivery Systems methods, Durapatite chemical synthesis, Folic Acid chemistry, Hep G2 Cells, Humans, Hydrogen-Ion Concentration, KB Cells, Mice, Neoplasms drug therapy, Cell Line, Tumor drug effects, Doxorubicin administration & dosage, Drug Carriers chemistry, Drug Carriers pharmacology, Durapatite chemistry, Nanoparticles chemistry
- Abstract
Nanoparticles coupled with targeting moieties have attracted a great deal of attention for cancer therapy since they can facilitate site-specific delivery of drug and significantly limit the side effects of systemic chemotherapy. In this study, our aim is to develop surface functionalized hydroxyapatite nanoparticles, which could provide binding sites for a cancer cell targeting ligand, folic acid (FA) as well as an anticancer drug, doxorubicin hydrochloride (DOX). In order to attain dual functionalities, hydroxyapatite nanoparticles were functionalized with gelatin molecules. Gelatin, being a protein has both carboxyl and amine moieties, which makes it suitable for binding of DOX and FA. FA was chemically conjugated to the nanoparticles through an EDCNHS coupling reaction. The formation of single-phase hydroxyapatite nanostructure was ascertained by X-ray diffraction studies and the presence of organic moieties on the surface of nanoparticles was evident from Fourier transform infrared spectroscopy, thermogravimetric analysis and U.V.-visible spectroscopy. The FA-conjugated nanoparticles (FA-Gel-HANPs) showed high affinity towards DOX and pH-responsive sustained release of drug with higher release rate under acidic pH conditions, desired for cancer therapy. The FA-Gel-HANPs showed negligible cytotoxicity towards different cell lines (HepG2, WEHI-164, KB, WI-26 VA4 and WRL-68). However, DOX loaded nanoparticles (DOX-FA-Gel-HANPs) exhibited significant toxicity towards these cells, which was however highest in folate receptor (FR)-overexpressing, KB cells. These results were correlated with enhanced cellular uptake of DOX-FA-Gel-HANPs in KB cells in comparison to FR-deficient, WRL-68 cells studied by confocal laser scanning microscopy and flow cytometry. Moreover, cell cycle analysis in KB cells, showed higher sub-G1 population, indicating apoptosis as one of the cell death mechanisms. Overall, this study suggests that DOX-FA-Gel-HANPs could serve as a promising tumor-targeted drug delivery system., Competing Interests: Declaration of Competing Interest There are no conflicts of interest to declare., (Copyright © 2019 Elsevier B.V. All rights reserved.)
- Published
- 2020
- Full Text
- View/download PDF
28. Estimation and in-situ detection of thorium in human liver cell culture by arsenazo-III based colorimetric assay.
- Author
-
Yadav R, Pandey BN, and Kumar A
- Subjects
- Colorimetry, Hep G2 Cells, Humans, Molecular Structure, Tumor Cells, Cultured, Arsenazo III chemistry, Coloring Agents chemistry, Thorium analysis
- Abstract
To understand the biological effects of Thorium-232 (Th) in human cells and animal models as well as to assess mitigation strategies for its detoxification, there is a need to develop a sensitive, specific, high-throughput and easily-implementable assay for detection and estimation of Th in biological samples. Here, we have optimized arsenazo-III dye based colorimetric assay to detect Th in biological samples. The concentration of arsenazo-III (i.e. 50 µM) was optimized, which can reliably estimate Th in the concentration range of 2.5 to 40 µM. The optimized assay can specifically detect Th without interference from other metal ions (La, Ce, U, Fe, Ca, Cu, Zn and Mn). A significant correlation (R
2 = 0.999) was found between arsenazo-III-based detection of Th and total reflection X-ray fluorescence. The conditions of present assay successfully estimated Th in cell culture medium, cell harvesting (trypsin-EDTA) solution and cell lysate obtained from human liver cell culture. Moreover, for the first time, we detected Th in-situ in adherent liver cells in culture after staining with arsenazo-III. This study confirms that Th can be specifically determined in biological samples using arsenazo-III with the sensitivity, which is relevant to thorium toxicity research.- Published
- 2020
- Full Text
- View/download PDF
29. Primary and secondary bystander effect and genomic instability in cells exposed to high and low linear energy transfer radiations.
- Author
-
Kanagaraj K, Rajan V, Pandey BN, Thayalan K, and Venkatachalam P
- Subjects
- Alpha Particles adverse effects, Coculture Techniques, Fibroblasts cytology, Fibroblasts metabolism, Fibroblasts radiation effects, Humans, Lymphocytes cytology, Lymphocytes metabolism, Lymphocytes radiation effects, X-Rays adverse effects, Bystander Effect radiation effects, Genomic Instability radiation effects, Linear Energy Transfer
- Abstract
Purpose: Non-Targeted effects (NTE), such as bystander effect (BE) and genomic instability (GI) challenge central dogma of radiation biology. Moreover, there is a need to understand its universality in different type of cells and radiation quality. Materials and method: To study BE (primary and secondary) and GI Human adult dermal fibroblast (HADF) and peripheral blood lymphocytes (PBL) were exposed to low fluence of
241 Am alpha (α) particle and 6 MV X-ray. The BE was carried out by means of co-culture methodology after exposing the cells to both types of radiation and damage was measured using micronucleus assay (MN) and chromosomal aberration assay (CA) in the p1 cells while the GI was followed up in their progeny. Results: A dose-dependent increase in DNA damages (MN and CA) was observed in directly irradiated and bystander cells. The magnitude of BE was higher (6 fold) in cells co-cultured with the α-irradiated cells than that of with X-irradiated cells. Cross exposure of both cell types confirms that radiation induced BE is cell type dependent. In addition, induced DNA damage persisted for a longer population doubling in α-particle irradiated cells. Conclusion: This work adds evidence to secondary bystander response generated from primary bystander normal cells and its dependence to radiation quality.- Published
- 2019
- Full Text
- View/download PDF
30. Tumorsphere assay provides a better in vitro method for cancer stem-like cells enrichment in A549 lung adenocarcinoma cells.
- Author
-
Balla MMS, Yadav HD, and Pandey BN
- Subjects
- A549 Cells, Biomarkers, Tumor metabolism, Cell Separation, Humans, Hyaluronan Receptors metabolism, Nanog Homeobox Protein metabolism, Neoplastic Stem Cells metabolism, Octamer Transcription Factor-3 metabolism, Pluripotent Stem Cells metabolism, In Vitro Techniques, Neoplastic Stem Cells pathology
- Abstract
Cancer stem cells (CSCs) have been implicated in growth, metastasis, recurrence and chemo-/radio-resistance in several cancer types. Despite a plenty of literature about different in vitro techniques to enrich/isolate CSCs, their comparative characterization for stemness is not well established. In the present study, cells obtained following three in vitro assays [clonogenic assay, tumorsphere assay (TSA) and single cell assay (SCA)] were compared for their cancer stem-like cell characteristics in human lung adenocarcinoma (A549) cells. Expression of the pluripotent (OCT4, NANOG) and lung cancer stem cell marker (CD166) genes were studied in these cells. Results showed that in comparison to cells obtained from routine culture (CC), the cells obtained from TSA showed significantly higher expression of OCT-4 and NANOG. These results were further validated with quantification of cell surface cancer stem cell markers i.e. CD44
+ /CD24- in the cells obtained from different methods, which were higher in TSA and SCA. Additionally, functional characterization of cancer stem-like cells (CSLCs) using ALDH assay showed the highest % of ALDH+ cells in TSA. These results were in agreement with higher resistance of these cells against 5-Fluorouracil suggesting higher fraction of CSLCs in TSA than the other assays. These results showed that TSA provides a better method to enrich CSLCs in A549 lung adenocarcinoma cells., (Copyright © 2019 Elsevier Ltd. All rights reserved.)- Published
- 2019
- Full Text
- View/download PDF
31. pH-Labile Magnetic Nanocarriers for Intracellular Drug Delivery to Tumor Cells.
- Author
-
Gawali SL, Barick KC, Shetake NG, Rajan V, Pandey BN, Kumar NN, Priyadarsini KI, and Hassan PA
- Abstract
We report the development of pH-labile ascorbic acid-coated magnetic nanocarriers (AMNCs) for effective delivery of the anticancer drug doxorubicin hydrochloride (DOX) to tumor cells. The uniqueness of this drug delivery system lies in the covalent conjugation of DOX through carbamate and hydrazone bonds, resulting in a slow and sustained drug release profile at different environmental acidities. X-ray diffraction and transmission electron microscopy analyses reveal the formation of crystalline single-phase Fe
3 O4 nanoparticles with an average size of 10 nm. The changes in the interfacial characteristics of the nanocarriers and the presence of organic coatings are probed by infrared spectroscopy, dynamic light scattering, zeta potential, and thermogravimetric measurements. AMNCs show high colloidal stability in aqueous and cell culture media and possess good magnetic field responsivity and protein resistance characteristics. The drug-loaded nanocarriers exhibited sustained pH-triggered release of drug molecules in acidic mediums, substantial cellular internalization, and significant toxicity toward the proliferation of mouse skin fibrosarcoma (WEHI-164), human breast cancer (MCF-7), and human lung cancer (A549) cells. However, it showed significantly lower toxicity in human normal lung (WI26VA) cells. Overall, these results suggest a pH-sensitive drug release of nanoformulations, which showed selective toxicity to tumor than normal cells., Competing Interests: The authors declare no competing financial interest.- Published
- 2019
- Full Text
- View/download PDF
32. Direct and bystander effects in human blood lymphocytes exposed to 241 Am alpha particles and the relative biological effectiveness using chromosomal aberration and micronucleus assay.
- Author
-
Karthik K, Rajan V, Pandey BN, Sivasubramanian K, Paul SFD, and Venkatachalam P
- Subjects
- Humans, Lymphocytes cytology, Metaphase genetics, Metaphase radiation effects, Micronucleus Tests, X-Rays adverse effects, Alpha Particles adverse effects, Americium adverse effects, Bystander Effect radiation effects, Chromosome Aberrations radiation effects, Lymphocytes metabolism, Lymphocytes radiation effects
- Abstract
Purpose: It is important to understand the significance of alpha (α) radiation-induced bystander effects (RIBE) and its relative biological effectiveness (RBE); this is because the phenomenon is not universal and the mechanism is unclear and because the RBE is widely varying and projected to be very high. Materials and methods: Isolated lymphocytes from healthy volunteers ( n = 10) were exposed to either low fluence α-particles (
241 Am), γ-rays (60 Co), or X-rays (225 kVp and 6 MV). Co-culture methodology was employed to investigate bystander effects (BEs). Chromosomal aberrations (CA) and micronucleus (MN) formation were used to study the BE and calculated RBE. Results: Lymphocytes directly exposed to the types of radiation used showed a dose-dependent increase in the frequency of CA and MN; dose independent increases in the frequency of these chromosomal damages in co-cultured bystander cells, implies that all three types of radiation-induced a BE. The calculated RBE at the level of 5% induced aberrations varied between 9 and 20. Conclusion: The magnitude of low fluence α-particle induced RIBE is higher than in low LET (linear energy transfer) radiation. The RBE also varies depending upon the endpoints used and adds up to targeted effects. Since the endpoint of CA is considered as an important and early marker of risk prediction, the RIBE and RBE using CA as a marker are relevant for radiation protection purposes.- Published
- 2019
- Full Text
- View/download PDF
33. Iron-oxide nanoparticles target intracellular HSP90 to induce tumor radio-sensitization.
- Author
-
Shetake NG, Kumar A, and Pandey BN
- Subjects
- Animals, Antineoplastic Agents chemistry, Apoptosis drug effects, Cell Cycle drug effects, Cell Line, Tumor, Cell Proliferation drug effects, Drug Screening Assays, Antitumor, Ferric Compounds chemistry, Fibrosarcoma metabolism, Fibrosarcoma pathology, HSP90 Heat-Shock Proteins metabolism, Humans, Kinetics, Mice, Radiation-Sensitizing Agents chemistry, Antineoplastic Agents pharmacology, Ferric Compounds pharmacology, Fibrosarcoma drug therapy, HSP90 Heat-Shock Proteins antagonists & inhibitors, Nanoparticles chemistry, Radiation-Sensitizing Agents pharmacology
- Abstract
Background: Nanoparticle-based therapies have emerged as a promising approach to overcome limitations of conventional chemotherapy. Present study investigates the potential of oleic acid-functionalized iron-oxide nanoparticles (MN-OA) to enhance the radiation response of fibrosarcoma tumor and elucidates its underlying mechanism., Methods: Various cellular and molecular assays (e.g. MTT, clonogenic, cell cycle analysis, cell death, DNA damage/repair) and tumor growth kinetics were employed to investigate the mechanism of MN-OA induced radio-sensitization., Results: Mouse (WEHI-164) and human (HT-1080) fibrosarcoma cells treated with MN-OA and gamma-radiation (2 Gy) showed a significant decrease in the cell proliferation. Combination treatment showed significant decrease in clonogenic survival of WEHI-164 cells and was found to induce cell cycle arrest, apoptosis and mitotic catastrophe. The mechanism of radio-sensitization was found to involve binding of MN-OA with HSP90, resulting in down-regulation of its client proteins, involved in cell cycle progression (Cyclin B1 and CDC2) and DNA-double strand break repair (e.g. RAD51 and BRCA1). Consistently, longer persistence of DNA damage in cells treated with MN-OA and radiation was observed in the form of γ-H2AX foci. The efficacy and mechanism of MN-OA-induced radio-sensitization was also validated in an immuno-competent murine fibrosarcoma model., Conclusion: This study reveals the key role of HSP90 in the mechanism of tumor radio-sensitization by MN-OA., General Significance: Present work provides a deeper understanding about the mechanism of MN-OA-induced tumor radiosensitization, highlighting the role of HSP90 protein. In addition to diagnostic and magnetic hyperthermia abilities, present remarkable radiosensitizing activity of MN-OA would further excite the clinicians to test its anti-cancer potential., (Copyright © 2019 Elsevier B.V. All rights reserved.)
- Published
- 2019
- Full Text
- View/download PDF
34. Thorium decorporation efficacy of rationally-selected biocompatible compounds with relevance to human application.
- Author
-
Ali M, Sadhu B, Boda A, Tiwari N, Das A, Musharaf Ali SK, Bhattacharya D, Pandey BN, and Kumar A
- Subjects
- Chelating Agents metabolism, Humans, Liver metabolism, Thorium blood, Biocompatible Materials metabolism, Thorium metabolism
- Abstract
During civil, nuclear or defense activities, internal contamination of actinides in humans and mitigation of their toxic impacts are of serious concern. Considering the health hazards of thorium (Th) internalization, an attempt was made to examine the potential of ten rationally-selected compounds/formulations to decorporate Th ions from physiological systems. The Th-induced hemolysis assay with human erythrocytes revealed good potential of tiron, silibin (SLB), phytic acid (PA) and Liv.52
® (L52) for Th decorporation, in comparison to diethylenetriaminepentaacetic acid, an FDA-approved decorporation drug. This was further validated by decorporation experiments with relevant human cell models (erythrocytes and liver cells) and biological fluid (blood) under pre-/post-treatment conditions, using inductively coupled plasma mass spectrometry (ICP-MS) and transmission electron microscopy (TEM). Furthermore, density functional theory-based calculations and extended X-ray absorption fine structure (EXAFS) spectroscopy confirmed the formation of Th complex by these agents. Amongst the chosen biocompatible agents, tiron, SLB, PA and L52 hold promise to enhance Th decorporation for human application., (Copyright © 2018 Elsevier B.V. All rights reserved.)- Published
- 2019
- Full Text
- View/download PDF
35. Synthesis and characterization of monodispersed water dispersible Fe 3 O 4 nanoparticles and in vitro studies on human breast carcinoma cell line under hyperthermia condition.
- Author
-
Sharma KS, Ningthoujam RS, Dubey AK, Chattopadhyay A, Phapale S, Juluri RR, Mukherjee S, Tewari R, Shetake NG, Pandey BN, and Vatsa RK
- Subjects
- Anisotropy, Breast Neoplasms pathology, Female, Ferric Compounds chemistry, Humans, Iron chemistry, MCF-7 Cells, Magnetic Fields, Magnetite Nanoparticles chemistry, Temperature, Water chemistry, Breast Neoplasms therapy, Ferric Compounds therapeutic use, Hyperthermia, Induced methods, Magnetite Nanoparticles therapeutic use
- Abstract
Monodispersed Fe
3 O4 magnetic nanoparticles (MNPs) having size of 7 nm have been prepared from iron oleate and made water dispersible by functionalization for biomedical applications. Three different reactions employing thioglycolic acid, aspartic acid and aminophosphonate were performed on oleic acid coated Fe3 O4 . In order to achieve a control on particle size, the pristine nanoparticles were heated in presence of ferric oleate which led to increase in size from 7 to 11 nm. Reaction parameters such as rate of heating, reaction temperature and duration of heating have been studied. Shape of particles was found to change from spherical to cuboid. The cuboid shape in turn enhances magneto-crystalline anisotropy (Ku ). Heating efficacy of these nanoparticles for hyperthermia was also evaluated for different shapes and sizes. We demonstrate heat generation from these MNPs for hyperthermia application under alternating current (AC) magnetic field and optimized heating efficiency by controlling morphology of particles. We have also studied intra-cellular uptake and localization of nanoparticles and cytotoxicity under AC magnetic field in human breast carcinoma cell line.- Published
- 2018
- Full Text
- View/download PDF
36. Receptor tyrosine kinase signaling in cancer radiotherapy and its targeting for tumor radiosensitization.
- Author
-
Bhattacharya P, Shetake NG, Pandey BN, and Kumar A
- Subjects
- Active Transport, Cell Nucleus, Apoptosis, Chemoradiotherapy, DNA Repair, Endocytosis, ErbB Receptors antagonists & inhibitors, Humans, Neoplasm Invasiveness, Neoplasms metabolism, Protein Transport radiation effects, Receptor, IGF Type 1 antagonists & inhibitors, Tumor Escape, Neoplasms radiotherapy, Protein Kinase Inhibitors therapeutic use, Radiation Tolerance, Receptor Protein-Tyrosine Kinases physiology, Signal Transduction physiology
- Abstract
Purpose: One of the most important implications of 'Radiation Biology' research is to improve cancer radiotherapy with minimum side effects. In this regard, combination of chemotherapy with radiation has significantly improved tumor control as well as overall survival in a variety of cancers. However, this has been achieved at the cost of significant normal tissue toxicity, due to the lack of specificity of chemotherapy. Membrane-localized receptor tyrosine kinases (RTKs) have been found to play a driving role in various hallmarks of cancer. Moreover, an early successful clinical trial using RTK-antagonist (cetuximab) to improve tumor radiosensitivity has led to an advancement in this field of research. However, a comprehensive review integrating these findings of various oncogenic RTKs, from basic radiobiology-to-radiotherapy clinical trials, is lacking in literature. Therefore, the present review analyses relevant in-vitro, in-vivo, preclinical/clinical studies and postulates the concept of 'Radiation Biology of RTKs in Cancer'., Conclusions: The present review elucidates the effect of IR on various oncogenic RTKs and their mechanisms, downstream signaling, intracellular translocations, their role in the repair of radiation-induced DNA damage and post-irradiation survival. Based on the knowledge derived from RTK biology and the analysis of relevant clinical trials, this review attempts to identify radiobiological considerations, which could be implemented in future trials, combining radiotherapy with RTK-antagonist. Additionally, we identify the radiosensitizing potential of recently developed RTK-targeted nanoformulations. This review would probably change the Radiation Oncologist's view for translation of tumor-specific radiosensitization in clinic.
- Published
- 2018
- Full Text
- View/download PDF
37. pH sensitive surfactant-stabilized Fe 3 O 4 magnetic nanocarriers for dual drug delivery.
- Author
-
Dutta B, Shetake NG, Barick BK, Barick KC, Pandey BN, Priyadarsini KI, and Hassan PA
- Subjects
- Animals, Antineoplastic Agents chemistry, Cell Line, Tumor, Curcumin chemistry, Doxorubicin chemistry, Drug Combinations, Drug Compounding methods, Fever drug therapy, Fibroblasts drug effects, Fibroblasts pathology, Hydrogen-Ion Concentration, Hydrophobic and Hydrophilic Interactions, Magnetic Fields, Magnetite Nanoparticles ultrastructure, Mice, Oleic Acid chemistry, Particle Size, Sodium Dodecyl Sulfate chemistry, Static Electricity, Surface-Active Agents chemistry, Antineoplastic Agents pharmacology, Curcumin pharmacology, Doxorubicin pharmacology, Drug Delivery Systems methods, Ferrosoferric Oxide chemistry, Magnetite Nanoparticles chemistry
- Abstract
Highly water-dispersible surfactant-stabilized Fe
3 O4 magnetic nanocarriers (SMNCs) were prepared by self-assembly of anionic surfactant, sodium dodecyl sulphate (SDS) on hydrophobic (oleic acid coated) nanoparticles and their biomedical applications were investigated. These nanocarriers have an average size of about 10nm and possess tunable surface charge properties. The formation of an organic coating of SDS was evident from infrared spectroscopy, dynamic light scattering, zeta-potential and thermogravimetric measurements. These nanocarriers were used for loading of both hydrophilic and hydrophobic anticancer agents such as doxorubicin hydrochloride (DOX) and curcumin (CUR), respectively. DOX was conjugated onto the surface of nanocarriers through electrostatic interaction, whereas CUR was encapsulated into the hydrophobic interlayer between oleic acid and SDS. The toxicity and cellular internalization of drug loaded nanocarriers were investigated against WEHI-164 cancer cell line. Specifically, the drug loading, pH sensitive drug release and cellular internalization studies suggested that these nanocarriers are suitable for dual drug delivery. Furthermore, they show good heating ability under AC magnetic field, thus can be used as effective heating source for hyperthermia treatment of cancer., (Copyright © 2017 Elsevier B.V. All rights reserved.)- Published
- 2018
- Full Text
- View/download PDF
38. Differential diagnosis of lung cancer, its metastasis and chronic obstructive pulmonary disease based on serum Vegf, Il-8 and MMP-9.
- Author
-
Balla MM, Desai S, Purwar P, Kumar A, Bhandarkar P, Shejul YK, Pramesh CS, Laskar S, and Pandey BN
- Subjects
- Aged, Aged, 80 and over, Biomarkers, Tumor blood, Case-Control Studies, Diagnosis, Differential, Female, Humans, Lung Neoplasms secondary, Male, Matrix Metalloproteinase 2 blood, Middle Aged, Interleukin-8 blood, Lung Neoplasms blood, Lung Neoplasms diagnosis, Matrix Metalloproteinase 9 blood, Pulmonary Disease, Chronic Obstructive blood, Pulmonary Disease, Chronic Obstructive diagnosis, Vascular Endothelial Growth Factor A blood
- Abstract
Chronic obstructive pulmonary disease (COPD) patients are at higher risk of developing lung cancer and its metastasis, but no suitable biomarker has been reported for differential diagnosis of these patients. Levels of serum biomarkers (VEGF, IL-8, MMP-9 and MMP-2) were analyzed in these patients, which were compared with healthy donors (HD). Levels of VEGF (P < 0.005) and MMP-9 (P < 0.05) were significantly higher in COPD patients than HD. Compared to HD, a decrease in IL-8 (~8.1 folds; P < 0.0001) but an increase in MMP-9 (~1.6 folds; P < 0.05) levels were observed in the lung cancer patients. Cancer patients showed significantly (P < 0.005) lower levels of serum VEGF (1.9 folds) and IL-8 (~9 folds) than the COPD patients. VEGF level was significantly higher (2.6 folds; P < 0.0005) in metastatic than non-metastatic cancer patients. However, MMP-2 didn't show significant variation in these patients. The Youden's index (YI) values for lung cancer diagnosis in HD using IL-8 was 0.55 with 83.3% overall accuracy. VEGF was able to diagnose COPD in HD with better YI (0.38) and overall accuracy (70.6%). IL-8 was able to diagnose cancer in COPD patients and HD with YI values of 0.35, 0.55 with 71% and 83.3% overall accuracy, respectively.
- Published
- 2016
- Full Text
- View/download PDF
39. Folic acid conjugated Fe 3 O 4 magnetic nanoparticles for targeted delivery of doxorubicin.
- Author
-
Rana S, Shetake NG, Barick KC, Pandey BN, Salunke HG, and Hassan PA
- Subjects
- Antineoplastic Agents administration & dosage, Cysteine chemistry, Doxorubicin administration & dosage, Drug Liberation, Endocytosis, Humans, Hydrogen-Ion Concentration, KB Cells, Microscopy, Electron, Transmission, Spectroscopy, Fourier Transform Infrared, Thermogravimetry, X-Ray Diffraction, Antineoplastic Agents chemistry, Doxorubicin chemistry, Drug Carriers chemistry, Folic Acid chemistry, Magnetite Nanoparticles chemistry
- Abstract
The interfacial engineering of magnetic nanoparticles (MNPs) with specific functional groups or targeting ligands is important for their in vivo applications. We report here the preparation and characterization of bifunctional magnetic nanoparticles (BMNPs) which contain a carboxylic moiety for drug binding and an amine moiety for folate mediated drug targeting. BMNPs were prepared by introducing bioactive cysteine molecules onto the surface of undecenoic acid coated Fe
3 O4 magnetic nanoparticles (UMNPs) via a thiol-ene click reaction and then, folic acid was conjugated with these BMNPs through an EDC-NHS coupling reaction. X-ray diffraction (XRD) and transmission electron microscopy (TEM) analysis indicate the formation of highly crystalline single-phase Fe3 O4 nanostructures. The changes in the interfacial characteristics of the nanoparticles and the presence of an organic coating are evident from Fourier transform infrared (FTIR) spectroscopy, dynamic light scattering (DLS), zeta-potential measurement, and thermogravimetric analysis (TGA). These nanocarriers have an average size of 10 nm, and have a pH dependent charge conversional feature and protein resistance characteristic in physiological medium. These nanoparticles also show high loading affinity for an anticancer drug, doxorubicin hydrochloride (DOX) and its pH dependent release. This is highly beneficial for cancer therapy as the relatively low pH in tumors will specifically stimulate the drug release at the site of interest. Furthermore, our fluorescence microscopy and flow cytometry studies confirmed the higher cellular internalization capability of these folic acid conjugated nanoparticles in cancer cells over-expressing folate receptors.- Published
- 2016
- Full Text
- View/download PDF
40. Molecular Understanding of Growth Inhibitory Effect from Irradiated to Bystander Tumor Cells in Mouse Fibrosarcoma Tumor Model.
- Author
-
Desai S, Srambikkal N, Yadav HD, Shetake N, Balla MM, Kumar A, Ray P, Ghosh A, and Pandey BN
- Subjects
- Animals, Apoptosis radiation effects, Cell Line, Tumor, Cellular Senescence, Female, Gamma Rays, Mice, Mice, Inbred BALB C, Mitotic Index, Neoplasm Transplantation, Neovascularization, Pathologic, Proteomics, Radiation Dosage, Radiotherapy, Signal Transduction, Bystander Effect radiation effects, Fibrosarcoma drug therapy, Fibrosarcoma radiotherapy
- Abstract
Even though bystander effects pertaining to radiation risk assessment has been extensively studied, the molecular players of radiation induced bystander effect (RIBE) in the context of cancer radiotherapy are poorly known. In this regard, the present study is aimed to investigate the effect of irradiated tumor cells on the bystander counterparts in mouse fibrosarcoma (WEHI 164 cells) tumor model. Mice co-implanted with WEHI 164 cells γ-irradiated with a lethal dose of 15 Gy and unirradiated (bystander) WEHI 164 cells showed inhibited tumor growth, which was measured in terms of tumor volume and Luc+WEHI 164 cells based bioluminescence in vivo imaging. Histopathological analysis and other assays revealed decreased mitotic index, increased apoptosis and senescence in these tumor tissues. In addition, poor angiogenesis was observed in these tumor tissues, which was further confirmed by fluorescence imaging of tumor vascularisation and CD31 expression by immuno-histochemistry. Interestingly, the growth inhibitory bystander effect was exerted more prominently by soluble factors obtained from the irradiated tumor cells than the cellular fraction. Cytokine profiling of the supernatants obtained from the irradiated tumor cells showed increased levels of VEGF, Rantes, PDGF, GMCSF and IL-2 and decreased levels of IL-6 and SCF. Comparative proteomic analysis of the supernatants from the irradiated tumor cells showed differential expression of total 24 protein spots (21 up- and 3 down-regulated) when compared with the supernatant from the unirradiated control cells. The proteins which showed substantially higher level in the supernatant from the irradiated cells included diphosphate kinase B, heat shock cognate, annexin A1, angiopoietin-2, actin (cytoplasmic 1/2) and stress induced phosphoprotein 1. However, the levels of proteins like annexin A2, protein S100 A4 and cofilin was found to be lower in this supernatant. In conclusion, our results provided deeper insight about the damaging RIBE in an in vivo tumor model, which may have significant implication in improvement of cancer radiotherapy., Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2016
- Full Text
- View/download PDF
41. Cellular and spectroscopic characterization of cancer stem cell-like cells derived from A549 lung carcinoma.
- Author
-
Balla MM, Ningthoujam RS, Kumar M, Bandekar JR, and Pandey BN
- Subjects
- Adenocarcinoma of Lung, Biomarkers, Cell Line, Tumor, Cell Survival radiation effects, Circular Dichroism, Humans, Neoplastic Stem Cells radiation effects, Oxidation-Reduction, Radiation Tolerance, Single-Cell Analysis, Spectroscopy, Fourier Transform Infrared, Superoxide Dismutase metabolism, Adenocarcinoma chemistry, Adenocarcinoma metabolism, Lung Neoplasms chemistry, Lung Neoplasms metabolism, Neoplastic Stem Cells chemistry, Neoplastic Stem Cells metabolism, Spectrum Analysis methods
- Abstract
Background: Cancer stem cells (CSCs) are increasingly being realized to play a significant role in the mechanism of chemo-, radio-resistance, and metastasis of cancer. However, studies for spectral markers of CSCs using Fourier transform infrared (FT-IR) and circular dichroism (CD) spectroscopy are limited in the literature., Materials and Methods: In the present study, CSCs obtained from single cell assay of human lung adenocarcinoma (A549) cells were characterized using CD44+/CD24-/low phenotype expression, Hoechst 33342 dye efflux assay, and expression of stemness genes. Spectral changes in cancer cells and clones enriched with CSCs were studied by FT-IR and CD spectroscopy., Results: The changes in FT-IR spectra of clones enriched with CSCs showed the difference in the secondary protein structure as compared to nonstem cancer cells. Moreover, A549 clone cells showed higher C-O band of carbohydrates and deoxyribose ring vibrations of Z-form of DNA. These results were further corroborated with CD spectroscopy that showed increased alpha helix proteins and difference in DNA conformation in clones enriched with CSCs. FT-IR studies also showed higher imidazole-metal interactions in clones enriched with CSCs. These results are in agreement with higher activity of one of the metalloproteins that is, superoxide dismutase in clones enriched with CSCs and their increased radioresistance., Conclusions and General Significance: Overall, these observations provide novel FT-IR and CD spectroscopy signatures in A549 clones enriched with CSCs, which may have implications in the quantifying magnitude of CSCs as prognostic markers in cancer therapy.
- Published
- 2016
- Full Text
- View/download PDF
42. The interaction of actinide and lanthanide ions with hemoglobin and its relevance to human and environmental toxicology.
- Author
-
Kumar A, Ali M, Ningthoujam RS, Gaikwad P, Kumar M, Nath BB, and Pandey BN
- Subjects
- Animals, Chironomidae, Ecotoxicology, Humans, Larva, Oxygen metabolism, Cerium toxicity, Hemoglobins metabolism, Lanthanum toxicity, Thorium toxicity, Uranium toxicity
- Abstract
Due to increasing use of lanthanides/actinides in nuclear and civil applications, understanding the impact of these metal ions on human health and environment is a growing concern. Hemoglobin (Hb), which occurs in all the kingdom of living organism, is the most abundant protein in human blood. In present study, effect of lanthanides and actinides [thorium: Th(IV), uranium: U(VI), lanthanum: La(III), cerium: Ce(III) and (IV)] on the structure and function of Hb has been investigated. Results showed that these metal ions, except Ce(IV) interacted with carbonyl and amide groups of Hb, which resulted in the loss of its alpha-helix conformation. However, beyond 75μM, these ions affected heme moiety. Metal-heme interaction was found to affect oxygen-binding of Hb, which seems to be governed by their closeness with the charge-to-ionic-radius ratio of iron(III). Consistently, Ce(IV) being closest to iron(III), exhibited a greater effect on heme. Binding constant and binding stoichiometry of Th(IV) were higher than that of U(VI). Experiments using aquatic midge Chironomus (possessing human homologous Hb) and human blood, further validated metal-Hb interaction and associated toxicity. Thus, present study provides a biochemical basis to understand the actinide/lanthanide-induced interference in heme, which may have significant implications for the medical and environmental management of lanthanides/actinides toxicity., (Copyright © 2015 Elsevier B.V. All rights reserved.)
- Published
- 2016
- Full Text
- View/download PDF
43. The interaction of human serum albumin with selected lanthanide and actinide ions: Binding affinities, protein unfolding and conformational changes.
- Author
-
Ali M, Kumar A, Kumar M, and Pandey BN
- Subjects
- Circular Dichroism, Humans, Protein Conformation, Spectrophotometry, Ultraviolet, Spectroscopy, Fourier Transform Infrared, Actinoid Series Elements chemistry, Lanthanoid Series Elements chemistry, Serum Albumin chemistry
- Abstract
Human serum albumin (HSA), the most abundant soluble protein in blood plays critical roles in transportation of biomolecules and maintenance of osmotic pressure. In view of increasing applications of lanthanides- and actinides-based materials in nuclear energy, space, industries and medical applications, the risk of exposure with these metal ions is a growing concern for human health. In present study, binding interaction of actinides/lanthanides [thorium: Th(IV), uranium: U(VI), lanthanum: La(III), cerium: Ce(III) and (IV)] with HSA and its structural consequences have been investigated. Ultraviolet-visible, Fourier transform-infrared, Raman, Fluorescence and Circular dichroism spectroscopic techniques were applied to study the site of metal ions interaction, binding affinity determination and the effect of metal ions on protein unfolding and HSA conformation. Results showed that these metal ions interacted with carbonyl (CO..:)/amide(N..-H) groups and induced exposure of aromatic residues of HSA. The fluorescence analysis indicated that the actinide binding altered the microenvironment around Trp214 in the subdomain IIA. Binding affinity of U(VI) to HSA was slightly higher than that of Th(IV). Actinides and Ce(IV) altered the secondary conformation of HSA with a significant decrease of α-helix and an increase of β-sheet, turn and random coil structures, indicating a partial unfolding of HSA. A correlation was observed between metal ion's ability to alter HSA conformation and protein unfolding. Both cationic effects and coordination ability of metal ions seemed to determine the consequences of their interaction with HSA. Present study improves our understanding about the protein interaction of these heavy ions and their impact on its secondary structure. In addition, binding characteristics may have important implications for the development of rational antidote for the medical management of health effects of actinides and lanthanides., (Copyright © 2016 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.)
- Published
- 2016
- Full Text
- View/download PDF
44. Relevance of radiobiological concepts in radionuclide therapy of cancer.
- Author
-
Kumar C, Shetake N, Desai S, Kumar A, Samuel G, and Pandey BN
- Subjects
- Apoptosis radiation effects, Cell Survival radiation effects, DNA Damage, Dose-Response Relationship, Radiation, Neoplasms pathology, Radiation Dosage, Radiopharmaceuticals therapeutic use, Models, Biological, Neoplasms physiopathology, Neoplasms radiotherapy, Radiobiology methods, Radioisotopes therapeutic use, Radiotherapy, Computer-Assisted methods
- Abstract
Purpose: Radionuclide therapy (RNT) is a rapidly growing area of clinical nuclear medicine, wherein radionuclides are employed to deliver cytotoxic dose of radiation to the diseased cells/tissues. During RNT, radionuclides are either directly administered or delivered through biomolecules targeting the diseased site. RNT has been clinically used for diverse range of diseases including cancer, which is the focus of the review., Conclusions: The major emphasis in RNT has so far been given towards developing peptides/antibodies and other molecules to conjugate a variety of therapeutic radioisotopes for improved targeting/delivery of radiation dose to the tumor cells. Despite that, many of the RNT approaches have not achieved their desired therapeutic success probably due to poor knowledge about complex and dynamic (i) fate of radiolabeled molecules; (ii) radiation dose delivered; (iii) cellular heterogeneity in tumor mass; and (iv) cellular radiobiological response. Based on understanding gathered during recent years, it may be stated that besides the absorbed dose, the net radiobiological response of tumor/normal cells also determines the clinical response of radiotherapeutic modalities including RNT. The radiosensitivity of tumor/normal cells is governed by radiobiological phenomenon such as radiation-induced bystander effect, genomic instability, adaptive response and low dose hyper-radiosensitivity. These concepts have been well investigated in the context of external beam radiotherapy, but their clinical implications during RNT have received meagre attention. In this direction, a few studies performed using in vitro and in vivo models envisage the possibilities of exploiting the radiobiological knowledge for improved therapeutic outcome of RNT.
- Published
- 2016
- Full Text
- View/download PDF
45. Effect of proton and gamma irradiation on human lung carcinoma cells: Gene expression, cell cycle, cell death, epithelial-mesenchymal transition and cancer-stem cell trait as biological end points.
- Author
-
Narang H, Kumar A, Bhat N, Pandey BN, and Ghosh A
- Subjects
- Biomarkers, Tumor biosynthesis, Biomarkers, Tumor genetics, Cell Cycle Checkpoints genetics, Cell Death genetics, Cell Death radiation effects, Epithelial-Mesenchymal Transition genetics, Humans, Hyaluronan Receptors biosynthesis, Hyaluronan Receptors genetics, Lung Neoplasms genetics, Lung Neoplasms pathology, MCF-7 Cells, Neoplasm Proteins biosynthesis, Neoplasm Proteins genetics, Cell Cycle Checkpoints radiation effects, Epithelial-Mesenchymal Transition radiation effects, Gamma Rays, Gene Expression Regulation radiation effects, Lung Neoplasms metabolism, Protons
- Abstract
Proton beam therapy is a cutting edge modality over conventional gamma radiotherapy because of its physical dose deposition advantage. However, not much is known about its biological effects vis-a-vis gamma irradiation. Here we investigated the effect of proton- and gamma- irradiation on cell cycle, death, epithelial-mesenchymal transition (EMT) and "stemness" in human non-small cell lung carcinoma cells (A549). Proton beam (3MeV) was two times more cytotoxic than gamma radiation and induced higher and longer cell cycle arrest. At equivalent doses, numbers of genes responsive to proton irradiation were ten times higher than those responsive to gamma irradiation. At equitoxic doses, the proton-irradiated cells had reduced cell adhesion and migration ability as compared to the gamma-irradiated cells. It was also more effective in reducing population of Cancer Stem Cell (CSC) like cells as revealed by aldehyde dehydrogenase activity and surface phenotyping by CD44(+), a CSC marker. These results can have significant implications for proton therapy in the context of suppression of molecular and cellular processes that are fundamental to tumor expansion., (Copyright © 2015 Elsevier B.V. All rights reserved.)
- Published
- 2015
- Full Text
- View/download PDF
46. Doxorubicin enhances (131)I-rituximab induced cell death in Raji cells.
- Author
-
Kumar C, Pandey BN, Samuel G, and Venkatesh M
- Subjects
- Blotting, Western, Burkitt Lymphoma drug therapy, Burkitt Lymphoma radiotherapy, Cell Proliferation drug effects, Cell Proliferation radiation effects, Doxorubicin administration & dosage, Drug Synergism, Flow Cytometry, Humans, Poly(ADP-ribose) Polymerases metabolism, RNA, Messenger genetics, Radiopharmaceuticals, Rituximab administration & dosage, Signal Transduction drug effects, Tumor Cells, Cultured, Antineoplastic Combined Chemotherapy Protocols pharmacology, Apoptosis drug effects, Apoptosis radiation effects, Burkitt Lymphoma pathology, Iodine Radioisotopes pharmacology, Radiation-Sensitizing Agents pharmacology
- Abstract
Aim: There are various therapeutic modalities of treatment for non-Hodgkin's lymphoma, but with certain limitations, hence, investigating the scope of combined therapeutic approach., Materials and Methods: In this article, cellular toxicity, apoptosis and expression of mitogen-activated protein kinase signaling pathway proteins were investigated in Raji cells preincubated with doxorubicin followed by (131)I-rituximab (rituximab radiolabeled with Iodine-131) treatment., Results: It was found that the (131)I-rituximab in combination with doxorubicin showed a higher amount of cell toxicity and apoptosis compared to respective controls. Expression of anti-apoptotic protein (B-cell lymphoma-extra-large) was downregulated and cleavage of poly (ADP-ribose) polymerase, a marker of apoptosis was higher in cells treated with doxorubicin (2 μg/mL) and 131 I-rituximab (P ≤ 0.05). Moreover, in these cells the basal level of expression of p42/44 and p38 were increased while its phosphorylation was decreased., Conclusion: These results suggest that doxorubicin has the potential to sensitize (131)I-rituximab induced cell death in Raji cells.
- Published
- 2015
- Full Text
- View/download PDF
47. Covalent bridging of surface functionalized Fe3O4 and YPO4:Eu nanostructures for simultaneous imaging and therapy.
- Author
-
Barick KC, Sharma A, Shetake NG, Ningthoujam RS, Vatsa RK, Babu PD, Pandey BN, and Hassan PA
- Subjects
- Cell Line, Tumor, Europium therapeutic use, Ferrosoferric Oxide therapeutic use, Humans, Hyperthermia, Induced, Luminescent Agents therapeutic use, Magnetic Fields, Magnetics, Magnetite Nanoparticles chemistry, Magnetite Nanoparticles therapeutic use, Nanostructures therapeutic use, Nanostructures ultrastructure, Neoplasms diagnosis, Neoplasms therapy, Optical Imaging, Yttrium therapeutic use, Europium chemistry, Ferrosoferric Oxide chemistry, Luminescent Agents chemistry, Nanostructures chemistry, Phosphates chemistry, Yttrium chemistry
- Abstract
Magnetic luminescent hybrid nanostructures (MLHN) have received a great deal of attention due to their potential biomedical applications such as thermal therapy, magnetic resonance imaging, drug delivery and intracellular imaging. We report the development of bifunctional Fe3O4 decorated YPO4:Eu hybrid nanostructures by covalent bridging of carboxyl PEGylated Fe3O4 and amine functionalized YPO4:Eu particles. The surface functionalization of individual nanoparticulates as well as their successful conjugation was evident from Fourier transform infrared (FTIR) spectroscopy, dynamic light scattering (DLS), zeta-potential and transmission electron microscopy (TEM) studies. X-ray diffraction (XRD) analysis reveals the formation of highly crystalline hybrid nanostructures. TEM micrographs clearly show the binding/anchoring of 10 nm Fe3O4 nanoparticles onto the surface of 100-150 nm rice grain shaped YPO4:Eu nanostructures. These MLHN show good colloidal stability, magnetic field responsivity and self-heating capacity under an external AC magnetic field. The induction heating studies confirmed localized heating of MLHN under an AC magnetic field with a high specific absorption rate. Photoluminescence spectroscopy and fluorescence microscopy results show optical imaging capability of MLHN. Furthermore, successful internalization of these MLHN in the cells and their cellular imaging ability are confirmed from confocal microscopy imaging. Specifically, the hybrid nanostructure provides an excellent platform to integrate luminescent and magnetic materials into one single entity that can be used as a potential tool for hyperthermia treatment of cancer and cellular imaging.
- Published
- 2015
- Full Text
- View/download PDF
48. Acetylamine derivative of diospyrin, a plant-derived binaphthylquinonoid, inhibits human colon cancer growth in Nod-Scid mice.
- Author
-
Hazra S, Ghosh S, Kumar A, Pandey BN, and Hazra B
- Subjects
- Animals, Antineoplastic Agents, Phytogenic pharmacology, Caspase 3 metabolism, Cell Cycle drug effects, Cell Line, Tumor, Cell Proliferation drug effects, Cell Proliferation radiation effects, Cell Survival drug effects, Colonic Neoplasms pathology, DNA Fragmentation, Humans, Membrane Potential, Mitochondrial, Mice, Inbred NOD, Mice, SCID, Naphthoquinones pharmacology, Tumor Burden drug effects, Xenograft Model Antitumor Assays, Antineoplastic Agents, Phytogenic therapeutic use, Colonic Neoplasms drug therapy, Naphthoquinones therapeutic use
- Abstract
Anticancer activity of diospyrin and its derivatives (1-5) was evaluated against thirteen human cell lines. Compared to diospyrin (1), the acetylamine derivative (4) exhibited increase in cytotoxicity, particularly in HT-29 colon cancer cells, showing GI50 values of 33.90 and 1.96 μM, respectively. Also, enhanced toxicity was observed when cells, pre-treated with compound 4, were exposed to radiation. In vivo assessment of 4 was undertaken on tumour-bearing Nod-Scid mice treated at 4 mg/kg/day. Significant reduction in relative tumour volume (~86-91 %) was observed during the 12th-37th days after drug treatment. Increased caspase-3 activity and DNA ladder formation was observed in HT-29 cells after treatment with 4, suggesting induction of apoptotic death after drug treatment. Moreover, flow cytometric determination of Annexin V- FITC positive and PI negative cells demonstrated 17.4, 26.4, and 27.9 % of early apoptosis, respectively, upon treatment with 5, 10 and 25 μM of 4. HT-29 cells after treatment with 4 (1-25 μM) revealed ~2.5- 3- folds generation of ROS. Furthermore, concentration dependent decrease of mitochondrial trans-membrane potential (∆ψm), and expression of Bcl-2/Bax and other marker proteins suggested involvement of mitochondrial pathway of cell death. Overall, our results demonstrated the underlying cell-death mechanism of the plant-derived naphthoquinonoid (4), and established it as a prospective chemotherapeutic 'lead' molecule against colon cancer.
- Published
- 2015
- Full Text
- View/download PDF
49. Magnetic nanoparticle-mediated hyperthermia therapy induces tumour growth inhibition by apoptosis and Hsp90/AKT modulation.
- Author
-
Shetake NG, Kumar A, Gaikwad S, Ray P, Desai S, Ningthoujam RS, Vatsa RK, and Pandey BN
- Subjects
- Animals, Apoptosis drug effects, Cell Line, Tumor, Combined Modality Therapy, Female, Fibrosarcoma metabolism, HSP90 Heat-Shock Proteins metabolism, Kidney metabolism, Liver metabolism, Lung metabolism, Magnetite Nanoparticles therapeutic use, Mice, Inbred BALB C, Proto-Oncogene Proteins c-akt metabolism, Spleen metabolism, Tissue Distribution, Tumor Burden drug effects, Fibrosarcoma drug therapy, Hyperthermia, Induced, Magnetite Nanoparticles administration & dosage
- Abstract
Purpose: We have evaluated the hyperthermia efficacy of oleic acid-functionalised Fe(3)O(4) magnetic nanoparticles (MN-OA) under in vivo conditions and elucidated the underlying mechanism of tumour growth inhibition., Materials and Methods: The efficacy and mechanism of tumour growth inhibition by MN-OA-mediated magnetic hyperthermia therapy (MHT) was evaluated in a murine fibrosarcoma tumour model (WEHI-164) using techniques such as TUNEL assay, Western blotting (WB), immunofluorescence (IF) staining and histopathological examination. In addition, bio-distribution of MN-OA in tumour/other target organs and its effect on normal organ function were studied by Prussian blue staining and serum biochemical analysis, respectively., Results: MN-OA-induced MHT resulted in significant inhibition of tumour growth as determined by measurement of tumour volume, as well as by in vivo imaging of tumour derived from luciferase-transfected WEHI-164 cells. Histopathology analysis showed presence of severe apoptosis and reduced tumour cells proliferation, which was further confirmed by TUNEL assay, reduced expression of Ki-67 and enhanced level of cleaved caspase-3, in tumours treated with MHT. Moreover, expression of heat stress marker, Hsp90 and its client protein, AKT/PKB was reduced by ∼50 and 80%, respectively, in tumours treated with MHT as studied by WB and IF staining. Serum analysis suggested insignificant toxicity of MN-OA (in terms of liver and kidney function), which was further correlated with minimal accumulation of MN-OA in target organs., Conclusions: These results suggest the involvement of apoptosis and Hsp90/AKT modulation in MN-OA-mediated MHT-induced tumour growth inhibition.
- Published
- 2015
- Full Text
- View/download PDF
50. Differential roles of ATF-2 in survival and DNA repair contributing to radioresistance induced by autocrine soluble factors in A549 lung cancer cells.
- Author
-
Desai S, Kumar A, Laskar S, and Pandey BN
- Subjects
- Activating Transcription Factor 2 genetics, Autocrine Communication genetics, Cell Line, Tumor, Cell Survival genetics, Cell Survival radiation effects, Cyclic AMP genetics, Cyclic AMP metabolism, Humans, Lung Neoplasms genetics, Lung Neoplasms pathology, MAP Kinase Kinase 4 genetics, MAP Kinase Kinase 4 metabolism, MAP Kinase Signaling System genetics, MAP Kinase Signaling System radiation effects, Neoplasm Proteins genetics, Radiation Tolerance genetics, p38 Mitogen-Activated Protein Kinases genetics, p38 Mitogen-Activated Protein Kinases metabolism, Activating Transcription Factor 2 metabolism, Autocrine Communication radiation effects, DNA Repair radiation effects, Gamma Rays, Lung Neoplasms metabolism, Neoplasm Proteins metabolism
- Abstract
Radioresistance is one of the obstacles to the effective radiotherapy for non-small cell lung cancer. Soluble factors in the tumour microenvironment are often implicated in radioresistance but the underpinning mechanism(s) remain largely elusive. We herein studied the wholesome effect of autocrine cytokines and growth factors in the form of self-conditioned medium (CM) on the radiosensitivity of A549 cells. A549 cells grown in CM exhibited radioresistance which was associated with increased survival and DNA repair. CM induced pro-survival pathways through increased intracellular cAMP and phosphorylation of JNK and p38. Downstream to JNK/p38 signalling, ATF-2 phosphorylated at Thr69/71 was accompanied with its increased transcriptional activity in CM treated cells. Pre-treatment with cAMP inhibitor and silencing of ATF-2 abrogated the CM-induced survival. Interestingly, in cells treated with CM followed by radiation, ATF-2 was found to be switched over from transcription factor to DNA damage response protein. In CM treated cells, after γ-radiation p-ATF-2(Thr69/71) and subsequently the transcriptional activity of ATF-2 were declined with simultaneous rise in p-ATF-2(Ser490/498). Immunoprecipitation/immunoblotting and inhibitor studies showed that phosphorylation of ATF-2 at Ser490/498 was mediated by ATM. Moreover, p-ATF-2(Ser490/498) was found to be co-localised with γ-H2AX in DNA repair foci in CM-treated cells. The DNA repair activity of ATF-2 was assisted with higher activity MRN complex in cells grown in CM. Our study revealed that, autocrine soluble factors regulate dual but differential role of ATF-2 as a transcription factor or DNA repair protein, which collectively culminate in radioresistance of A549 cells., (Copyright © 2014 Elsevier Inc. All rights reserved.)
- Published
- 2014
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.