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[Display omitted] The excessive secretion of H 2 O 2 within cells is closely associated with cellular dysfunction. Therefore, high sensitivity in situ detection of H 2 O 2 released from living cells was valuable in clinical diagnosis. In the present work, a novel electrochemical cells sensing platform by synthesizing copper nanoclusters (CuNCs) at room temperature based on DNA nanoribbon (DNR) as a template (DNR-CuNCs). The tight and ordered arrangement of nanostructured assemblies of DNR-CuNCs conferred the sensor with superior stability (45 days) and electrochemical performance. The MUC1 aptamer extending from the DNR template enabled the direct capture MCF-7 cells on electrode surface, this facilitated real-time monitoring of H 2 O 2 release from stimulated MCF-7 cells. While the captured MCF-7 cells on the electrode surface significantly amplified the current signal of H 2 O 2 release compared with the traditional electrochemical detection H 2 O 2 released signal by MCF-7 cells in PBS solution. The approach provides an effective strategy for the design of versatile sensors and achieving monitored cell release of H 2 O 2 in long time horizon (10 h). Thereby expanding the possibilities for detecting biomolecules from live cells in clinical diagnosis and biomedical applications. [ABSTRACT FROM AUTHOR]

Breast cancer is a leading cause of cancer-related deaths among women. Cisplatin is used for treatment, but the development of resistance in cancer cells is a significant concern. This study aimed to investigate changes in the transcriptomes of cisplatin-resistant MCF7 cells. We conducted RNA sequencing of cisplatin-resistant MCF7 cells, followed by differential expression analysis and bioinformatic investigations to identify changes in gene expression and modified signal transduction pathways. We examined the size and quantity of extracellular vesicles. A total of 724 genes exhibited differential expression, predominantly consisting of protein-coding RNAs. Notably, two long non-coding RNAs (lncRNAs), NEAT1 and MALAT, were found to be dysregulated. Bioinformatic analysis unveiled dysregulation in processes related to DNA synthesis and repair, cell cycle regulation, immune response, and cellular communication. Additionally, modifications were observed in events associated with extracellular vesicles. Conditioned media from resistant cells conferred resistance to wild-type cells in vitro. Furthermore, there was an increase in the number of vesicles in cisplatin-resistant cells. Cisplatin-resistant MCF7 cells displayed differential RNA expression, including the dysregulation of NEAT1 and MALAT long non-coding RNAs. Key processes related to DNA and extracellular vesicles were found to be altered. The increased number of extracellular vesicles in resistant cells may contribute to acquired resistance in wild-type cells. [ABSTRACT FROM AUTHOR]

Doxorubicin is the first-line chemotherapy agent for breast cancer treatment. However, it's reported to cause cardiotoxicity and induce chemoresistance in breast cancer cells. Doxorubicin is able to induce Pgp (P-glycoprotein) overexpression through NF-kB activation resulting in efflux of chemotherapeutic agents in MCF-7 cells. One of the approaches being developed for cancer treatment is combination therapy by combining two or more anticancer agents that may reduce side effects and provide better effects than single therapy. Peperomia pellucida is reported to have anticancer activity and is widely used as a traditional medicine. This study aimed to investigate the cytotoxic activity of the n-hexane fraction of Peperomia pellucida (NFP) and its combination with doxorubicin (D) against MCF-7 cells. The selectivity of NFP was evaluated using vero cells as a comparator. The phytochemical properties of NFP were evaluated using TLC and LC-MS/MS methods. The cytotoxic activity was determined using the MTT assay. Combination Index (CI) calculations were performed to determine the effect of the combination. This study found that NFP contained about 30 identified compounds and had an IC 50 of 96.68 ppm, while doxorubicin had an IC 50 of 2.10 ppm. The combination of 24.2 ppm (1/4 IC 50) of NFP with 0.26 ppm (1/8 IC 50) of doxorubicin had a synergistic cytotoxic effect (CI=0.6) against MCF-7 cells. NFP was selective for MCF-7 cells with a selectivity index of 21.83. The results suggest that NFP may have the potential to enhance the therapeutic efficacy of doxorubicin in breast cancer treatment. [Display omitted] • The N-hexane fraction of Peperomia pellucida (NFP) contained about 30 identified compounds, including ß-sitosterol and stigmasterol. • The N-hexane fraction of Peperomia pellucida (NFP) was selective for MCF-7 cells with IC 50 of 96,68. • The combination of the N-hexane fraction of Peperomia pellucida (NFP) (1/4 IC 50) with doxorubicin (1/8 IC 50) had a synergistic effect with a CI value of 0.6 and increased cytotoxic activity against MCF-7 cells. [ABSTRACT FROM AUTHOR]

Cannabis sativa is a well-known plant for its psychoactive effects; however, its many derivatives, such as Cannabidiol (CBD), contain several therapeutic applications. Tetrahydrocannabinol (THC) is the main cannabis derivative responsible for psychoactive properties, while CBD is non-psychotropic. For this reason, CBD has been more exploited in the last decade. CBD has been connected to multiple anticancer properties, and when combined with photodynamic therapy (PDT), it is possible to eradicate tumors more effectively. In this study, CBD was utilized to treat MCF-7 breast cancer cells, followed by in vitro PDT combination therapy. Conventional breast cancer treatment modalities such as chemotherapy, radiotherapy, etc. have been reported for inducing a number of undesirable side effects, recurrence of the disease, and low quality of life. In this study, cells were exposed to varying concentrations of CBD (i.e., 1.25, 2.5, 5, 10, and 20 μg/mL) and incubated 12 and 24 h after treatment. The optimal doses were then used in combination therapy. Morphology and biochemical assays, including lactate dehydrogenase (LDH) for membrane integrity, adenosine triphosphate (ATP) for viability, and trypan blue exclusion assay for viability, were used to examine cellular responses after treatments. The optimal concentration was then utilized in Hypericin-Gold nanoparticles mediated PDT combination. The results revealed that, in a dose-dependent manner, conventional morphological characteristics of cell death, such as vacuolization, blebbing, and floating were observed in treated cells. The biochemical responses demonstrated an increase in LDH, a decrease in ATP, and a reduction in viability. This study demonstrated that CBD induces cell death in MCF-7 breast cancer cells cultured in vitro. The immunofluorescence results of combination therapy indicated that cell death occurred via apoptosis. In conclusion, this study proposes that the CBD and PDT combination therapy is effective in killing MCF-7 breast cancer cells in vitro by induction of apoptosis. [ABSTRACT FROM AUTHOR]

Senescence due to exogenous and endogenous stresses triggers metabolic reprogramming and is associated with many pathologies, including cancer. In solid tumors, senescence promotes tumorigenesis, facilitates relapse, and changes the outcomes of anti-cancer therapies. Hence, cellular and molecular mechanisms regulating senescent pathways make attractive therapeutic targets. Cancer cells undergo metabolic reprogramming to sustain the growth-arrested state of senescence. In the present study, we aimed to understand the metabolic reprogramming in MCF-7 breast tumor cells in response to two independent inducers of DNA damage-mediated senescence, including ionizing radiation and doxorubicin. Increased DNA double-strand breaks, as demonstrated by γH2AX staining, showed a senescence phenotype, with expression of senescence-associated β-galactosidase accompanied by the upregulation of p21 and p16 in both groups. Further, untargeted analysis of the senescence-related extracellular metabolome profile of MCF-7 cells showed significantly reduced concentrations of carnitine and pantothenic acid and increased levels of S-adenosylhomocysteine in doxorubicin-treated cells, indicating the accumulation of ROS mediated DNA damage and impaired mitochondrial membrane potential. Similarly, a significant decline in the creatine level was observed in radiation-exposed cells, suggesting an increase in oxidative stress-mediated DNA damage. Our study, therefore, provides key effectors of the metabolic changes in doxorubicin and radiation-induced early senescence in MCF-7 breast cancer cells. • X-ray and doxorubicin increased the accumulation of ROS and mitochondrial dysfunction to maintain the senescence phenotype. • Extracellular metabolic profiling delineates dysregulation in critical effectors for sustaining the senescence phenotype. • Pathway enrichment analysis showed increased perturbation in various bioenergetic pathways related to oxidative stress. • These deregulated biochemical pathways may aid as important biosignatures for the robust improvement of treatment strategies. [ABSTRACT FROM AUTHOR]

Background: Multi-drug resistance is an important challenge in the chemotherapy of cancer. The role of annexin A5 (ANXA5) in the biology of cancer has been the focus of many studies. Breast Cancer (BC) is frequent cancer in women with high morbidity and mortality rate. The present study aimed to investigate the effects of ANXA5 overexpression on the anti-tumor activity of Epirubicin (EPI) in MCF-7 and MCF-7/ADR cells. Methods: MCF-7 and MCF-7/ADR cells were transfected with the pAdenoVator-CMV-ANXA5-IRES-GFP plasmid or mock plasmid. The overexpression of ANXA5 was evaluated using qPCR. The effects of ANXA5 overexpression and EPI on the cell viability of MCF-7 and MCF-7/ADR cells were measured using an MTT assay. Cell apoptosis was measured by annexin V/7-AAD flow cytometry assay. Results: Following the overexpression of ANXA5, the viability of MCF-7 and MCF-7/ADR was significantly decreased. Furthermore, the overexpression of ANXA5 in MCF-7 cells increased the cytotoxic effects of EPI in all doses and reduced the IC50 of EPI from 17.69 µM to 4.07 µM. Similarly, the overexpression of ANXA5 in MCF7-ADR cells reduced the IC50 of EPI from 27.3 µM to 6.69 µM. ANXA5 overexpression alone or combined with EPI treatment increased the apoptosis of MCF7 and MCF7-ADR cells. Conclusion: The results of the present study demonstrate that ANXA5 overexpression increases the sensitivity of MCF-7 and MCF-7/ADR to EPI, suggesting a possible beneficial role of ANXA5 in the therapy of BC. [ABSTRACT FROM AUTHOR]

Thiadiazole derivatives have garnered significant attention in the field of medicinal chemistry due to their diverse pharmacological activities, including anticancer properties. This article presents the synthesis of a series of thiadiazole derivatives and investigates their chemical characterization and potential anticancer effects on various cell lines. The results of the nuclear magnetic resonance (NMR) analyses confirmed the successful formation of the target compounds. The anticancer potential was evaluated through in silico and in vitro cell-based assays using LoVo and MCF-7 cancer lines. The assays included cell viability, proliferation, apoptosis, and cell cycle analysis to assess the compounds' effects on cancer cell growth and survival. Daphnia magna was used as an invertebrate model for the toxicity evaluation of the compounds. The results revealed promising anticancer activity for several of the synthesized derivatives, suggesting their potential as lead compounds for further drug development. The novel compound 2g, 5-[2-(benzenesulfonylmethyl)phenyl]-1,3,4-thiadiazol-2-amine, demonstrated good anti-proliferative effects, exhibiting an IC50 value of 2.44 µM against LoVo and 23.29 µM against MCF-7 after a 48-h incubation and little toxic effects in the Daphnia test. [ABSTRACT FROM AUTHOR]

Urinary tract infection is an infectious disease that requires immediate treatment. It can occur in any age group and involves both genders equally. The present study was to check the resistance of some antibiotics and to assess the antibacterial potential of three extracts of three plants against notorious bacteria involved in urinary tract infections. Along with assessing the antibacterial activity of plant extracts, we checked for the anticancer potential of these extracts against the cancer cell lines MCF-7 and A2780. Cancer is the leading cause of mortality in developed countries. Determinations of total flavonoid content, total phenolic content, total alkaloid content, total tannin content, total carotenoid content, and total steroid content were performed. The disk diffusion method was used to analyze the antibacterial activity of plant extracts. Ethanolic extract of Selenicereus undatus showed sensitivity (25–28 mm) against bacteria, whereas chloroform and hexane extracts showed resistance against all bacteria except Staphylococcus (25 mm). Ethanolic extract of Pistacia vera L. showed sensitivity (22–25 mm) against bacteria, whereas chloroform and hexane extracts showed resistance. Ethanolic extract of Olea europaea L. showed sensitivity (8–16 mm) against all bacteria except Staphylococcus, whereas chloroform and hexane extracts showed resistance. Positive controls showed variable zones of inhibition (2–60 mm), and negative control showed 0–1 mm. The antibiotic resistance was much more prominent in the case of hexane and chloroform extracts of all plants, whereas ethanolic extract showed a sensitivity of bacteria against extracts. Both cell lines, MCF-7 and A2780, displayed decreased live cells when treated with plant extracts. [ABSTRACT FROM AUTHOR]

The researchers are working hard to discover eco-friendly alternatives to chemically synthesized metal nanoparticles. The current study used Corchorus aestuans to evaluate bio-synthesis, physiochemical characterization and antimicrobial activities against human pathogenic bacteria and also the anticancer activity. The bio-synthesized Corchorus aestuans silver nanoparticles (CA-AgNPs) were characterized by UV, FT-IR, powder XRD, FE-SEM, EDAX, HR-TEM, DLS and Zeta potential. The MTT assay also demonstrated improved cytotoxicity against bosom malignant breast cancer (MCF-7) cell lines with IC50 value of 56.47 μg/mL. The CA-AgNPs were also found to be antimicrobial effective against Gram-positive and Gram-negative bacteria and fungi. Furthermore, after 48 h of interaction, the bio-synthesized CA-AgNPs successfully degraded the Methylene Blue (MB) dye by nearly 91.19%. [ABSTRACT FROM AUTHOR]

Objective(s): Controlled drug delivery using nanotechnology enhances drug targeting at the site of interest and prevents drug dispersal throughout the body. This study focused on loading a poorly water-soluble drug tamoxifen (TMX) into silica nanoparticles (SNPs) and amine-functionalized mesoporous silica nanoparticles (NH2-SBA-15). Materials and Methods: SNPs were prepared according to the Stöber method and functionalized with an amine group using 3-aminopropyl triethoxysilane (APTES) through a one-pot synthesis method to produce amine-functionalized mesoporous silica nanoparticles (NH2-SBA-15). Characterization of both nanoparticles was performed using FT-IR, FE-SEM, CHN analysis, porosity tests (BET), and dynamic light scattering (DLS). Results: The results showed an average particle size of 103.7 nm for SNPs and 225.9 nm for NH2-SBA-15. Based on the BET results, the pore size of NH2-SBA-15 was about 5.4 nm. In both silica nanoparticles, drug release at pH=5.7 was greater than that of pH=7.4. However, Tamoxifen-loaded NH2-SBA-15 (TMX@NH2-SBA-15) indicated the highest drug release in the acidic medium among TMX-loaded SNPs (TMX@SNPs), perhaps due to the high columbic repulsion in the functionalized NH2-SBA-15 nanoparticles. Regarding cytotoxicity results against MCF-7 breast cancer cell lines, both TMX@SNPs and TMX@NH2-SBA-15 nanoparticles exhibited greater cytotoxicity compared to the free TMX as a positive control. Although TMX@SNPs had a small size and high loading capacity, the cytotoxic effects were higher than those of TMX@NH2-SBA-15. Conclusion: Amine functionalization of SNPs can improve the potential activity of these nanoparticles for target therapy. [ABSTRACT FROM AUTHOR]

Background: Discovering new cytotoxic compounds has received significant attention due to the rise in drug resistance and the adverse effects associated with chemotherapy drugs. In this study, the cytoplasmic extract of Lactobacillus casei was used to produce iron oxide nanoparticles (Fe2o3 NPs), and the cytotoxic effects of NPs were investigated on MCF-7 and human embryonic kidney 293 (HEK-293) cells. Methods: The cytoplasmic extract of L. casei was mixed with 10³M iron sulfate solution and incubated for 3 weeks at 37 °C and 5% CO2. The coprecipitation method was used to synthesize chemical Fe2o3 NPs. The synthesis of NPs was studied by electron microscopy and X-ray diffraction (XRD) analysis, and the cytotoxic effects were evaluated with dilutions (10, 100, and 1000 µg/mL) on MCF-7 and HEK cells. Results: X-ray diffraction analysis and scanning electron microscopy presented the mean of NPs synthesized by the green method to be about 15 nm and their shape to be spherical, as well as the average of chemically synthesized NPs to be about 20 nm with cubic structure. Chemical and green synthesized NPs only at a concentration of 1000 µg/mL were able to significantly reduce the survival rate of normal HEK-293 cells; chemically synthesized NPs decreased MCF-7 cell survival only at 1000 µg/mL and green synthesis at 100 µg/mL and 1000 µg/mL. Conclusion: Generating Fe2o3 NPs is biologically safe using the green synthesis method and the cytoplasmic extract of L. casei, which may be a suitable candidate for the treatment of cancer cells. [ABSTRACT FROM AUTHOR]

Simple Summary: The burden of breast cancer has been increasing at an alarming rate. Epidemiological and empirical evidence has shown the key roles of vitamin D in the mitigation of tumor burden. But, the mechanisms by which vitamin D induces tumor reduction are poorly understood. Therefore, in the current study, we have aimed at understanding the role of vitamin D in inhibiting breast cancer progression in in vitro and in vivo models. The results of this study showed that vitamin D inhibited the proliferation of breast cancer cell lines in vitro and retarded Ehrlich ascites carcinomas in mice by inducing apoptosis as well as by halting cell cycle progression and angiogenesis. Future studies should focus more on strategies to improve the therapeutic index and the retention of vitamin D in tumor cells for better and long-lasting treatment. The incidence of aggressive and resistant breast cancers is growing at alarming rates, indicating a necessity to develop better treatment strategies. Recent epidemiological and preclinical studies detected low serum levels of vitamin D in cancer patients, suggesting that vitamin D may be effective in mitigating the cancer burden. However, the molecular mechanisms of vitamin D3 (cholecalciferol, vit-D3)-induced cancer cell death are not fully elucidated. The vit-D3 efficacy of cell death activation was assessed using breast carcinoma cell lines in vitro and a widely used Ehrlich ascites carcinoma (EAC) breast cancer model in vivo in Swiss albino mice. Both estrogen receptor-positive (ER+, MCF-7) and -negative (ER-, MDA-MB-231, and MDA-MB-468) cell lines absorbed about 50% of vit-D3 in vitro over 48 h of incubation. The absorbed vit-D3 retarded the breast cancer cell proliferation in a dose-dependent manner with IC50 values ranging from 0.10 to 0.35 mM. Prolonged treatment (up to 72 h) did not enhance vit-D3 anti-proliferative efficacy. Vit-D3-induced cell growth arrest was mediated by the upregulation of p53 and the downregulation of cyclin-D1 and Bcl2 expression levels. Vit-D3 retarded cell migration and inhibited blood vessel growth in vitro as well as in a chorioallantoic membrane (CAM) assay. The intraperitoneal administration of vit-D3 inhibited solid tumor growth and reduced body weight gain, as assessed in mice using a liquid tumor model. In summary, vit-D3 cytotoxic effects in breast cancer cell lines in vitro and an EAC model in vivo were associated with growth inhibition, the induction of apoptosis, cell cycle arrest, and the impediment of angiogenic processes. The generated data warrant further studies on vit-D3 anti-cancer therapeutic applications. [ABSTRACT FROM AUTHOR]

Aim. To evaluate an impact of different S6K1 isoforms expression in MCF-7 cells on initiation of Epithelial to Mesenchymal Transition (EMT). Methods. Immunocytochemical analysis, Real-Time PCR, Western blot. Results. We have demonstrated that unbalanced expression of p60, p70 and p85-S6K1 isoforms in MCF-7, namely downregulation of p70 and p85, and basal p60 expression, mediated by the CRISPR-Cas9 gene editing resulted in altered morphology and increased cell motility. Such changes were associated with the expression of genes whose products are involved in the regulation of cell motility, interaction with the extracellular matrix and loss of cellular adhesion demonstrating their increased potential for invasion and metastatic activity. qPCR analysis confirmed increased expression of a whole spectrum of genes associated with mesenchymal characteristics and loss of epithelial specific markers. Additionally, we observed a complete repression of the estrogen receptor 1 (ESR1) expression and downregulation of HER2/NEU (ERBB2). Conclusions. Our data demonstrate for the first time the implication of S6K1 isoforms in the regulation of EMT in MCF-7 cells by triggering for the concomitant onset of a series of possibly parallel events that changes the cell from an epithelial to a mesenchymal type and has a strong negative impact on ESR1 expression. At the tumor level that can mean breast tumor transition to a more aggressive most probably triple negative molecular subtype. [ABSTRACT FROM AUTHOR]

Oxidative stress and chronic inflammation interplay with the pathogenesis of cancer. Breast cancer in women is the burning issue of this century, despite chemotherapy and magnetic therapy. The management of secondary complications triggered by post-chemotherapy poses a great challenge. Thus, identifying target-specific drugs with anticancer potential without secondary complications is a challenging task for the scientific community. It is possible that green technology has been employed in a greater way in order to fabricate nanoparticles by amalgamating plants with medicinal potential with metal oxide nanoparticles that impart high therapeutic properties with the least toxicity. Thus, the present study describes the synthesis of Titanium dioxide nanoparticles (TiO2 NPs) using aqueous Terenna asiatica fruit extract, with its antioxidant, anti-inflammatory and anticancer properties. The characterisation of TiO2 NPs was carried out using a powdered X-ray diffractometer (XRD), Fourier transform infrared (FTIR), scanning electron microscopy (SEM), energy-dispersive X-ray diffraction (EDX), high-resolution transmission electron microscopy (HR-TEM), dynamic light scattering (DLS), and zeta-potential. TiO2 NPs showed their antioxidant property by scavenging 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radicals in a dose-dependent manner with an IC50 value of 80.21 µg/µL. To ascertain the observed antioxidant potential of TiO2 NPs, red blood cells (RBC) were used as an in vitro model system. Interestingly, TiO2 NPs significantly ameliorated all the stress parameters, such as lipid peroxidation (LPO), protein carbonyl content (PCC), total thiol (TT), superoxide dismutase (SOD), and catalase (CAT) in sodium nitrite (NaNO2)-induced oxidative stress, in RBC. Furthermore, TiO2 NPs inhibited RBC membrane lysis and the denaturation of both egg and bovine serum albumin, significantly in a dose-dependent manner, suggesting its anti-inflammatory property. Interestingly, TiO2 NPs were found to kill the MCF-7 cells as a significant decrease in cell viability of the MCF-7 cell lines was observed. The percentage of growth inhibition of the MCF-7 cells was compared to that of untreated cells at various doses (12.5, 25, 50, 100, and 200 µg/mL). The IC50 value of TiO2 NPs was found to be (120 µg/mL). Furthermore, the Annexin V/PI staining test was carried out to confirm apoptosis. The assay indicated apoptosis in cancer cells after 24 h of exposure to TiO2 NPs (120 µg/mL). The untreated cells showed no significant apoptosis in comparison with the standard drug doxorubicin. In conclusion, TiO2 NPs potentially ameliorate NaNO2-induced oxidative stress in RBC, inflammation and MCF-7 cells proliferation. [ABSTRACT FROM AUTHOR]

Magnesium oxide nanoparticles (MgONPs) synthesized by efficient green approach have unique physiochemical properties. In this study, MgONPs are synthesized with bract extract of Musa acuminate, an agro waste. The surface plasmon resonance at 450 nm in UV spectrum and FTIR peaks at 601 and 890 cm−1 confirmed the presence of MgONPs. XRD pattern revealed high crystallinity of the nanoparticles with an intense orientation peak at 111, and the size was 13 nm. The particles were spherical with an average size of 24.85 nm. The elemental percentage of magnesium and oxygen were 68.55% and 31.45%. MgONPs had antibacterial activity against Bacillus subtilis, Escherichia coli, Vibrio harveyi, Vibrio parahemolyticus, and Staphylococcus aureus with MIC, 6 μg/mL. The IC50 value for MCF‐7 cell was 113.56 μg/mL, and the normal cell line was 785.69 μg/mL. The NPs also exhibited hemolytic features in a dose‐dependent manner. The MgONPs exhibited photocatalytic degradation of methyl violet, CBB G‐250, and malachite green in 60 min duration. MgONPs had promising antibacterial, cytotoxic, hemolytic, photocatalytic, and seed germination activity. They have the potential to serve as an additive in a variety of biological applications. [ABSTRACT FROM AUTHOR]

Introduction: Breast cancer, as the most common malignancy among women, is shown to have a high mortality rate and resistance to chemotherapy. Research has shown the possible inhibitory role of Mesenchymal stem cells in curing cancer. Thus, the present work used human amniotic fluid mesenchymal stem cell-conditioned medium (hAFMSCs-CM) as an apoptotic reagent on the human MCF-7 breast cancer cell line. Methods: Conditioned medium (CM) was prepared from hAFMSCs. After treating MCF-7 cells with CM, a number of analytical procedures (MTT, realtime PCR, western blot, and flow cytometry) were recruited to evaluate the cell viability, Bax and Bcl-2 gene expression, P53 protein expression, and apoptosis, respectively. Human fibroblast cells (Hu02) were used as the negative control. In addition, an integrated approach to meta-analysis was performed. Results: The MCF-7 cells' viability was decreased significantly after 24 hours (P < 0.0001) and 72 hours (P < 0.05) of treatment. Compared with the control cells, Bax gene's mRNA expression increased and Bcl-2's mRNA expression decreased considerably after treating for 24 hours with 80% hAFMSCs-CM (P = 0.0012, P < 0.0001, respectively); an increasing pattern in P53 protein expression could also be observed. The flow cytometry analysis indicated apoptosis. Results from literature mining and the integrated meta-analysis showed that hAFMSCs-CM is able to activate a molecular network where Bcl2 downregulation stands in harmony with the upregulation of P53, EIF5A, DDB2, and Bax, leading to the activation of apoptosis. Conclusion: Our finding demonstrated that hAFMSCs-CM presents apoptotic effect on MCF-7 cells; therefore, the application of hAFMSCs-CM, as a therapeutic reagent, can suppress breast cancer cells' viabilities and induce apoptosis. [ABSTRACT FROM AUTHOR]

Aseries of indole derivatives 1—3 have been synthesized in moderate to good yields by a one-pot, three-component cyclocondensation reaction of thiobarbituric acid, substituted aromatic aldehyde, and indole. The new indole compounds were fully characterized by FT-IR and NMR spectroscopy and mass spectrometry. The purity of compounds was characterized by elemental analysis and melting points. Indole derivatives were examined for their activity against three types of test bacteria and against breast cancer cells (MCF-7), human lung epithelial cells (A549), head and neck cancer cells (HNSCC). Compound 1 exhibited promising effective antiproliferative activity against breast cancer cells (MCF-7), human lung epithelial cells (A549), and head and neck cancer cells (HNSCC) compared with normal cells, and produced specific effect against Escherichia coli rather than against Klebsiella pneumonia and Staphylococcus aureus strains. Compound 3 showed anti-bacterial effect against E. coli and S. aureus isolated from the oral cavity while compound 2 had no effect against all three types of test bacteria. [ABSTRACT FROM AUTHOR]

Mitochondrial oxidative phosphorylation (OXPHOS) system dysfunction in cancer cells has been exploited as a target for anti-cancer therapeutic intervention. The downregulation of CR6-interacting factor 1 (CRIF1), an essential mito-ribosomal factor, can impair mitochondrial function in various cell types. In this study, we investigated whether CRIF1 deficiency induced by siRNA and siRNA nanoparticles could suppress MCF-7 breast cancer growth and tumor development, respectively. Our results showed that CRIF1 silencing decreased the assembly of mitochondrial OXPHOS complexes I and II, which induced mitochondrial dysfunction, mitochondrial reactive oxygen species (ROS) production, mitochondrial membrane potential depolarization, and excessive mitochondrial fission. CRIF1 inhibition reduced p53-induced glycolysis and apoptosis regulator (TIGAR) expression, as well as NADPH synthesis, leading to additional increases in ROS production. The downregulation of CRIF1 suppressed cell proliferation and inhibited cell migration through the induction of G0/G1 phase cell cycle arrest in MCF-7 breast cancer cells. Similarly, the intratumoral injection of CRIF1 siRNA-encapsulated PLGA nanoparticles inhibited tumor growth, downregulated the assembly of mitochondrial OXPHOS complexes I and II, and induced the expression of cell cycle protein markers (p53, p21, and p16) in MCF-7 xenograft mice. Thus, the inhibition of mitochondrial OXPHOS protein synthesis through CRIF1 deletion destroyed mitochondrial function, leading to elevated ROS levels and inducing antitumor effects in MCF-7 cells. [ABSTRACT FROM AUTHOR]

It was previously identified that there may be an active metabolite of bisphenol A (BPA), 4-methyl-2,4-bis(4-hydroxyphenyl)pent-1-ene (MBP). An in vitro system was developed to detect MBP toxicity to the Michigan Cancer Foundation-7 (MCF-7) cells that had been repeatedly exposed to a low dose of the metabolite. MBP profoundly activated estrogen receptor (ER)-dependent transcription as a ligand, with an EC 50 of 2.8 nM. Women are continuously exposed to numerous estrogenic environmental chemicals; but their susceptibility to these chemicals may be significantly altered after menopause. Long-term estrogen-deprived (LTED) cells, which display ligand-independent ER activation, are a postmenopausal breast cancer model derived from MCF-7 cells. In this study, we investigated the estrogenic effects of MBP on LTED cells in a repeated exposure in vitro model. The results suggest that i) nanomolar levels of MBP reciprocally disrupt the balanced expression of ERα and ERβ proteins, leading to the dominant expression of ERβ, ii) MBP stimulates ERs-mediated transcription without acting as an ERβ ligand, and iii) MBP utilizes mitogen-activated protein kinase and phosphatidylinositol-3 kinase signaling to evoke its estrogenic action. Moreover, the repeated exposure strategy was effective for detecting low-dose estrogenic-like effects caused by MBP in LTED cells. ● A bisphenol A metabolite, MBP, activates endocrine-resistant LTED cells. ● Repeated exposure methodology enables us to detect low-dose effects of MBP. ● MBP disrupts the balanced expression of ERα/β proteins, which leads to dominant ERβ. ● MBP stimulates ERs-mediated transcription without acting as a ligand for ERβ. ● MBP utilizes both MAPK and PI3K signaling to elicit ERβ-driven estrogenic action. [ABSTRACT FROM AUTHOR]

Human health is experiencing several obstacles in the modern medical era, particularly cancer. As a result, the cancer therapeutic arsenal should be continually expanded with innovative small molecules that preferentially target tumour cells. In this study, we describe the development of two small molecule series (7a–d and 12a–e) based on the 1-benzyl-5-bromoindolin-2-one scaffold that connected through a hydrazone linker to a 4-arylthiazole (7a–d) or 4-methyl-5-(aryldiazenyl)thiazole (12a–e) moiety. The anticancer activity of all the reported indolin-2-one derivatives was assessed against breast (MCF-7) and lung (A-549) cancer cell lines. The 4-arylthiazole-bearing derivatives 7c and 7d revealed the best anticancer activity toward MCF-7 cells (IC50 = 7.17 ± 0.94 and 2.93 ± 0.47, respectively). Furthermore, the VEGFR-2 inhibitory activity for 7c and 7d was evaluated. Both molecules disclosed good inhibitory activity, and their IC50 values were equal to 0.728 µM and 0.503 µM, respectively. Additionally, the impacts of 7d on the cell cycle phases as well as on the levels of different apoptotic markers (caspase-3, caspase-9, Bax, and Bcl-2) were assessed. Molecular docking and dynamic simulations are carried out to explore the binding mode of 7d within the VEGFR-2 active site. [ABSTRACT FROM AUTHOR]

Introduction: Worldwide, breast cancer is the most common cancer in women and is the main cause of death among all neoplasia in this group. Luminal A breast cancer represents approximately 70% of all breast cancers and is treated with hormone therapies targeting estrogen receptor alpha (ERα). Unfortunately, patients develop drug resistance leading to recurrence of neoplasia due to estrogen-independent ERα reactivation. Therefore, it is crucial to identify new molecular targets downstream ERα signaling pathway that allows the implementation of better treatments to improve the outcome of breast cancer patients. Overexpression of c-Fos, an ERα gene target, has been associated with increased cell motility, malignancy, metastasis, and invasion while its neutralization results in decreased breast cancer tumorigenesis. The aryl hydrocarbon receptor (AHR) ligands halogenated and polycyclic aromatic hydrocarbons, highly toxic compounds, down regulate c-Fos and ERα levels. The present study aimed to evaluate whether 6-formylindolo(3,2-b)carbazole (FICZ), a no toxic AHR agonist, modifies c-Fos levels in MCF-7 mammary carcinoma cells as well as to determine its effects on cell proliferation and migration. In addition, the possible mechanism through which FICZ mediates c-Fos levels in MCF-7 cells was investigated. Methods: Initially, the effect of FICZ on c-Fos mRNA and protein levels in MCF-7 cells, untreated or treated with estradiol, was evaluated by qPCR and Western blot. 2,3,7,8-Tetrachloro-dibenzo-p-dioxin, an AHR prototype agonist, was used as a positive control. Next, we examined the effect of FICZ on MCF-7 cell proliferation and migration by cell counting, MTT, 3H-thymidine incorporation, and scratch-wound assays. Finally, the involvement of proteasome 26S on ERα and c-Fos protein degradation was investigated by the use of MG132 and Western blot. Results: The data show that FICZ treatment downregulates c-Fos mRNA and protein levels, most likely by promoting ERα proteasome degradation, blocking MCF-7 cell proliferation and migration. The results also demonstrate that liganded ERα was required for FICZ-mediated ERα degradation. Conclusions: Activation of AHR results in a decreased MCF-7 cell proliferation and migration by ERα and c-Fos down regulation. Targeting AHR might be a promising therapy for breast cancer treatment, particularly when estrogen-independent ERα reactivation presents. [ABSTRACT FROM AUTHOR]

Background: We hypothesized that the antitumor effects of asiaticoside on breast cancer are driven by its ability to decrease the expression of tumor inflammation-promoting genes and increase apoptotic signaling. In this study, we aimed to better understand the mechanisms of action of asiaticoside as a chemical modulator or as a chemopreventive agent in breast cancer. Methods: MCF-7 cells were cultured and treated with 0, 20, 40, and 80 μM asiaticoside for 48 h. Fluorometric caspase-9, apoptosis, and gene expression analyses were conducted. For the xenograft experiments, we divided nude mice into the following 5 groups (10 animals per group): group I, control mice; group II, untreated tumor-bearing nude mice; group III, tumor-bearing nude mice treated with asiaticoside at weeks 1–2 and 4–7 and injected with MCF-7 cells at week 3; group IV, tumor-bearing nude mice injected with MCF-7 cells at week 3 and treated with asiaticoside beginning at week 6; and group V, nude mice treated with asiaticoside, as a drug control. After treatment, weight measurements were performed weekly. Tumor growth was determined and analyzed using histology and DNA and RNA isolation. Results: In MCF-7 cells, we found that asiaticoside increased caspase-9 activity. In the xenograft experiment, we found that TNF-α and IL-6 expression decreased (p < 0.001) via the NF-κB pathway. Conclusion: Overall, our data suggest that asiaticoside produces promising effects on tumor growth, progression, and tumor-associated inflammation in MCF-7 cells as well as a nude mouse MCF-7 tumor xenograft model. [ABSTRACT FROM AUTHOR]

Fe3O4/Au/porous Au nanohybrids being bi-functional nanoparticles with magnetic properties and high porosity, were synthesized and used for drug delivery. To achieve this purpose, after Fe3O4 nanoparticles synthesis, a gold layer coats them to increase their stability. Then, to improve the loading capacity of Fe3O4/Au nanoparticles, a shell of porous gold was synthesized on the Fe3O4/Au surface by creating an Ag-Au nanohybrid layer on Fe3O4/Au and dissolving the metallic silver atoms in HNO3 (0.01 M). The DLS results show that the synthesized nanohybrid has an average size of 68.0 ± 7.7 nm and a zeta potential of − 28.1 ± 0.2 mV. Finally, doxorubicin (DOX), as a pharmaceutical agent, was loaded onto the Fe3O4/Au/porous Au nanohybrids. The prepared nano-drug enhanced the therapeutic efficacy of DOX on MCF-7 cancer cells compared to the free DOX. These results confirmed a 1.5 times improvement in the antitumor activity of DOX-loaded Fe3O4/Au/porous Au nanohybrids. [ABSTRACT FROM AUTHOR]

Breast cancer is the most commonly diagnosed cancer and a leading cause of cancer-related death among women worldwide. Somatostatin (SST) and Cannabinoids have an anti-proliferative and pro-apoptotic effect, but the mechanisms of their actions remain elusive. In the present study, we have evaluated the effects of SST, Cannabidiol (CBD) alone or in combination on receptor expression, cell proliferation and apoptosis and related downstream signalling pathways in MDA-MB-231 and MCF-7 breast cancer cells. The results presented here demonstrate the cell type and agonist-dependent changes in receptor expression at the cell membrane, inhibition of cell proliferation and increased apoptosis following treatment with SST and CBD alone and in combination. In comparison to MDA-MB-231 cells, MCF-7 cells treated with SST alone and in combination with CBD exhibited inhibition of phosphorylated Protein Kinase B (pAKT) and phosphorylated-Phosphoinositide 3-Kinase (pPI3K) expression. Importantly, inhibition of PI3K/AKT activation was accompanied by enhanced PTEN expression in MCF-7 cells. These results highlight the possible interaction between SSTR and CBR subtypes with the implication in the modulation of receptor expression, cell viability and signal transduction pathways in a breast cancer cell type-dependent manner. • Breast cancer is the leading cause of cancer-related death among women worldwide. • Somatostatin and Cannabinoids displayed an anti-proliferative and pro-apoptotic effect in the cancer cell lines. • SST with or without CBD exhibited inhibition of signalling pathways associated with cell proliferation. • Our results indicate the possibility of SSTRs and CBRs crosstalk as novel therapeutic target in breast cancer treatment. [ABSTRACT FROM AUTHOR]

MicroRNA 193a-3p (miR193a-3p) is a short non-coding RNA with tumor suppressor properties. Breast cancer (BC) progression is governed by active interaction between breast cancer cells, vascular (V)/lymphatic (L) endothelial cells (ECs), and BC secretome. We have recently shown that miR193a-3p, a tumor suppressor miRNA, inhibits MCF-7 BC cell-driven growth of VECs via direct antimitogenic actions and alters MCF-7 secretome. Since LEC-BC cross-talk plays a key role in BC progression, we investigated the effects of miR193a-3p on MCF-7 secretome and estradiol-mediated growth effects in LECs and LEC + MCF-7 spheroids, and delineated the underlying mechanisms. Transfection of LECs with miR193a-3p, as well as secretome from MCF-7 transfected cells, inhibited LEC growth, and these effects were mimicked in LEC + MCF-7 spheroids. Moreover, miR193a-3p inhibited ERK1/2 and Akt phosphorylation in LECs and LEC + MCF-7 spheroids, which are importantly involved in promoting cancer development and metastasis. Treatment of LECs and LEC + MCF-7 spheroids with estradiol (E2)-induced growth, as well as ERK1/2 and Akt phosphorylation, and was abrogated by miR193a-3p and secretome from MCF-7 transfected cells. Gene expression analysis (GEA) in LEC + MCF-7 spheroids transfected with miR193a-3p showed significant upregulation of 54 genes and downregulation of 73 genes. Pathway enrichment analysis of regulated genes showed significant modulation of several pathways, including interferon, interleukin/cytokine-mediated signaling, innate immune system, ERK1/2 cascade, apoptosis, and estrogen receptor signaling. Transcriptomic analysis showed downregulation in interferon and anti-apoptotic and pro-growth molecules, such as IFI6, IFIT1, OSA1/2, IFITM1, HLA-A/B, PSMB8/9, and PARP9, which are known to regulate BC progression. The cytokine proteome array of miR193a-3p transfected MCF secretome and confirmed the upregulation of several growth inhibitory cytokines, including IFNγ, Il-1a, IL-1ra, IL-32, IL-33, IL-24, IL-27, cystatin, C-reactive protein, Fas ligand, MIG, and sTIM3. Moreover, miR193a-3p alters factors in MCF-7 secretome, which represses ERK1/2 and Akt phosphorylation, induces pro-apoptotic protein and apoptosis in LECs, and downregulates interferon-associated proteins known to promote cancer growth and metastasis. In conclusion, miR193a-3p can potentially modify the tumor microenvironment by altering pro-growth BC secretome and inhibiting LEC growth, and may represent a therapeutic molecule to target breast tumors/cancer. [ABSTRACT FROM AUTHOR]

Bioactive dihydropyrimidinones (DHPs) were designed and synthesized by a multicomponent Biginelli reaction. The reaction was catalyzed by the polarized surface of nano-zirconium dioxide with partial positive charge of 0.52e at the Zr center and a negative charge of −0.23e at the oxygen center. There was good corroboration between the computed and experimental ZrO2 cell parameters and bond distances as determined by in silico and in vitro experimental methods. Since DHPs were found to target the peroxisome proliferator-activated receptor (PPAR)-γ, we tested these ligands toward MCF-7 cell toxicity, which revealed that the compounds 4d [ethyl-4-(4′-fluoro-[1,1′-biphenyl]-4-yl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate] and 4e [ethyl-4-(3′-methoxy-[1,1′-biphenyl]-4-yl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate] inhibited proliferation with IC50 values of 11.8 and 15.8 μM, respectively. Further, our bioinformatic analysis found that the active molecule 4d, fit into the enzyme's catalytic site, almost in the same position as rosiglitazone, which was buried deep inside the cavity. In conclusion, we herein report novel DHPs which could be better structures to help explore a new class of synthetic PPAR-γ ligands. [ABSTRACT FROM AUTHOR]

The current study investigated the bio-synthesis of silver nanoparticles (AgNPs) through the use of leaf extract of Rhaphidophora pertusa. Visual confirmation of the formation of bio-synthesized R.pertusa silver nanoparticles (RP-AgNPs) came from observing the colour development of the colloidal AgNPs. Additionally, the characterization of AgNPs through FTIR, HR-SEM, EDAX, XRD, HR-TEM and DLS was carried out. At 424 nm, the presence of AgNPs was confirmed by UV–vis spectra. FTIR reveals the secondary molecules of R.pertusa which were bound with AgNPs containing -OH and -NH functional groups. The synthesized particles' sizes are validated by HR-TEM as approximately 19 nm, whereas EDAX investigations substantiated the existence of AgNPs. The FCC crystallinity of the synthesized RP-AgNPs was confirmed by the XRD report. The antioxidant response for the bio-synthesized RP-AgNPs was determined by DPPH assay. RP-AgNPs exhibited well inhibitory with 77.53% at 500 µg/mL. Furthermore, it was found that RP-AgNPs have good antibacterial activity on gram-positive (5.1 ± 1.82574 mm for Staphylococcus aureus) and gram-negative (3.1 ± 1.8257 mm for E.coli) bacteria for 10 µL/mL. The research shows that the MCF-7 cell proliferation is effectively inhibited by the synthesized RP-AgNPs with IC50 seen at 102.4 μg/mL. As a result, the present research findings have enormous potential for the delivery of medication. [ABSTRACT FROM AUTHOR]

Targeting cancer metabolic processes has increased interest over the last century. Cancer cells have an enhanced proliferation rate that requires high quantities of amino acids, including arginine. Therefore, arginine deprivation by L-arginase impairs tumor growth resulting in cell death. In the present study, L-arginine amidinohydrolase (L-arginase) from Streptomyces diastaticus was purified successfully by heat treatment, ethanol precipitation, and Sephadex G75–120 column. The molecular mass of the purified enzyme was 39 kDa. It showed maximum activity at pH 9.0 and a temperature of 50 °C. Moreover, the enzyme stability was observed at temperatures up to 50 °C and a pH range of 7.5 to 9.0. Then, the potential cytotoxicity of L-arginase was examined. L-arginase has an IC50 value of 595 μg/ml for MCF-7 (breast adenocarcinoma cells), 915 μg/ml for HepG2 (hepatocellular carcinoma cells), and 1200 μg/ml for SW620 cells (colorectal carcinoma cells) at 72 h post-treatment. Noteworthy, MCF-7 showed the lowest IC50 value of arginase treatment, therefore was further investigated for the underlying cytotoxic mechanisms using flow cytometric analysis of cell-cycle distribution, apoptosis, and autophagy. Moreover, SI values indicating a high selective cytotoxicity of arginase toward MCF-7 cells. L-arginase induced significant cell cycle arrest at the G1 phase, and no apparent apoptosis was detected. Interestingly, arginine deprivation by arginase leads to a prominent activation of autophagy in the apoptosis defected MCF-7 cells. Moreover, treatment with arginase significantly attenuated MCF-7 cell migration compared with control medium-treated cells. Collectively, L-arginase might potentially be involved in treating breast cancer. [Display omitted] [ABSTRACT FROM AUTHOR]

Objective(s): Nanotechnology has helped a lot in diagnosing and treating multiple illnesses, specifically cancer, and increasing the development of targeted drug delivery methods. Nanocomposites are materials with at least one component smaller than 100 nm. Therefore, this study aims to assess the anticancer effects of silver-graphene nanocomposite on MCF-7. Materials and Methods: In this study, the rate of inhibition of cancer cell growth and production of reactive oxygen radicals, malondialdehyde, and glutathione stores in MCF7 cells were investigated. Cancer cells were exposed to nano particles for 48 hr. Silver nanoparticles and graphene both reduced the growth rate of MCF-7. Results: Subsequently, by treating the cells with silver-graphene nanocomposite, the rate of inhibition of cell growth at the highest concentration was 84.60%. Nanoparticles also inhibited the growth of cancer cells through the oxidative stress pathway by increasing the amount of intracellular ROS, followed by increasing malondialdehyde and decreasing glutathione stores, so that at the highest combined concentration of nanoparticles, the amounts of LPO and ROS increased up to 70% and 74 %, and glutathione reserves decreased by 16%. Conclusion: Treatment of MCF-7 cells with silver or graphene nanoparticles and combination treatment with these two substances against cisplatin have sound effects, and by affecting oxidative stress factors, such as increased ROS and subsequent increase in lipid membrane damage, inhibit cell growth and proliferation. According to the mathematical model, silver graphene nanocomposite> silver nanoparticles> graphene has the best effect in inhibiting the growth of cancer cells, respectively. [ABSTRACT FROM AUTHOR]

Simple Summary: Cancer is a dramatic illness that ranks among the most pressing health concerns facing humanity and necessitates a proactive approach to treatment. Phytochemicals are regarded as interesting molecules for the development of anticancer drugs due to their pleiotropic effects on broad targets. The actions of phytochemicals are focused on tumor cells alone, with no negative effects on normal cells. The intricate process of carcinogenesis involves numerous signaling cascades. This study examined the effects of four organ extracts from a Mediterranean endemic plant, Cladanthus mixtus, on human tumor cells. To the best of our knowledge, this is the first study on this plant from northern Morocco showing relevant antiproliferative activity against two cancer cell lines and one non-tumoral cell line. Many of the chemotherapeutic drugs for the treatment of cancer are molecules identified and isolated from plants or their synthetic derivatives. This work aimed to identify the bioactive compounds using LC-MS and GC-MS and to evaluate the anticancer activity of the methanolic extracts of roots, stems, leaves, and flowers from Cladanthus mixtus. The anticancer activity was evaluated in vitro against two cancer cell lines: human breast carcinoma (MCF-7) and human prostate carcinoma (PC-3), using the MTT assay and microscopic observation. A human normal lung fibroblast (MRC-5) was included to determine the extract's safety for non-tumoral cells. The chemical composition results by LC-MS analysis revealed the presence of 24 phenolic compounds. Furthermore, GC-MS analysis allowed the identification of many biomolecules belonging to terpenoids, esters, alcohols, alkanes, fatty acids, organic acids, benzenes, phenols, ketones, carbonyls, amines, sterols, and other groups. The findings suggest that the majority of C. mixtus extracts have antiproliferative activity against two cancer cell lines, MCF-7 and PC-3, and one non-tumoral cell line, MRC-5. The activity was dose-dependent, and the highest effect was obtained with leaf extract in the two cancer cell lines. Moreover, these extracts demonstrated an acceptable toxicological profile against normal cells. Overall, C. mixtus extracts revealed promising antitumor properties provided by their phytochemical composition. [ABSTRACT FROM AUTHOR]

Objective: To investigate the anticancer effect of Illicium verum against human breast cancer MCF-7 cell line. Methods: An experimental study was conducted in Multidisciplinary and Tissue Culture Laboratory, Aga Khan University in collaboration with Pharmacology Department of Bahria University Medical and Dental College, Karachi, Pakistan from January 2021 to June 2021. MCF-7 cells of Luminal-A breast cancer were seeded in 96-well plate and treated with I.verum methanol extract. After incubation, MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) dye was used for cell viability and cell proliferation assays to determine the number of dead and viable cells, and the absorbance was measured using an enzyme-linked immunosorbent assay (ELISA) plate reader. In cell viability assay, different doses of I. verum methanol extract were used to treat the MCF-7 (0.25, 0.5, 1, 3, 6, 12, 25, and 50µg/ml) cells. For apoptosis analysis, the cells were processed with 4´, 6-diamidino-2-phenylindole fluorescent nuclear dye (DAPI) and were examined for fluorescence intensity and apoptotic cells. For cell proliferation assay and apoptosis the IC50 dose of 5.5µg/ml I. verum methanol extract was used. Results: The MCF-7 cells showed a significant reduction (p-value <0.01) in cell viability in the presence of all tested doses of I. verum methanol extract, except for the dose of 0.25µg/ml. The IC50 dose 5.5µg/ml of same extract also showed a significant reduction (p-value <0.01) in cell proliferation and apoptosis induction in MCF-7 cells. Conclusions: Illicium verum methanol extract possesses very potent anticancer action against MCF-7 cells through cytotoxicity, reduction, and inhibition of cancer cells and by inducing apoptosis. [ABSTRACT FROM AUTHOR]

The purpose of current research was to assess the apoptotic effects of biofabrication silver nanoparticles (AgNPs) mediated by the aqueous extract of Phlomis armeniaca on human breast cancer cells (MCF-7 and MDA-MB-231) in monolayer (2D) and spheroid (3D) cultures. The biosynthesized AgNPs were characterized by UV–Vis spectrophotometer (the peaks of resonances at 432 nm), scanning electron microscopy (SEM) and energy-dispersive X-ray spectrometry (EDS). 1–20 µM/mL AgNPs were applied to MCF-7 and MDA-MB-231 cell lines to determine IC50 values at 24, 48 and 72nd h and were found to be 10 µM/mL for both cell lines. Immunohistochemical staining results of BrdU, TUNEL, caspase-3 and Endo G in both 2D and 3D cultures and gene expression levels of caspases (caspase-3, -8 and -9) and Endo G were evaluated. Moreover, the total oxidant/antioxidant status (TOS–TAS) due to AgNPs application in both cell culture mediums was evaluated. AgNPs treatment results in both cell lines in both 2D and 3D cultures showed a significant decrease in the BrdU labeling index, while large amounts of cells were labelled with TUNEL and Endo G. In 2D culture, Endo G expression increased in MCF-7 cells at 48 and 72nd hours, while it increased significantly in MDA-MB-231 cells at all hours. OSI results show that ROS production is increased in cell medium treated with AgNPs. In conclusion, AgNPs mediated by Phlomis armeniaca, synthesized by a green method, successfully induced damage to mitochondria, resulting in cell cycle arrest and consequent cell proliferation blockade and death in both MCF-7 and MDA-MB-231 cells. [ABSTRACT FROM AUTHOR]

Breast cancer is recognized as the most common cause of cancer deaths in women. So far, no definite treatment has been identified there is no certain cure for breast cancer. The over expression of interleukin-8 is associated with increased tumor growth and breast cancer metastasis. Hesperetin is a flavonone sub-group of flavonoids that is abundantly found in citrus fruits, including lemons and oranges. Considering the anticancer and anti-inflammatory role of hesperetin, as also, well as the role of interleukin-8 in cancer metastasis and progression, in this study the present study aimed to assess, the effect of hesperetin on the expression of the interleukin-8 gene in MCF-7 cell line has been investigated. The relative expression level of interleukin-8 gene in MCF-7 cell line at concentrations of 0, 25, 50, 100, and 200 µM hesperetin and durations of 6, 24, and 48 hours (with the concentration of 100 µM) was performed using the A real-time polymerase chain reaction (real-time PCR)Real-time method PCR was performed. The obtained our results pointed out showed that the level of interleukin-8 gene expression decreases with an increase in by increasing the concentration of hesperetin (up to 100 µM), the level of interleukin-8 gene expression decreases. Furthermore, the level of interleukin-8 gene expression in the 48-hour treatment was also lower than that in the 24- and 6-hour treatments. Considering its various properties, including anti-cancer and anti-inflammatory properties, hesperetin could be effective in reducing the risk of metastasis and progression of breast cancer by reducing the expression of the interleukin-8 gene. [ABSTRACT FROM AUTHOR]

Background: The effect of conditioned medium on apoptosis and invasion of MCF-7 is still debated. Carnosic acid, a component of rosemary extract, is also reported to have anti-cancer property. Therefore, we studied the occurrence of apoptosis through AIF-dependent pathway in MCF-7 cells treated with conditioned medium and rosemary extract by evaluating the expression of AIF, P53, Bcl-2 and Bax genes. Method and Materials: In this studty, the experimental groups were: cultured MCF7 cells in medium containing serum (control), cultured cells in conditioned medium containing serum (CM group), cultured cells in medium containing different concentrations of rosemary extract (50 and 100 μg / ml) for 24 and 48 hours (treatment groups). The cell proliferation rate was studied by MTT test. Gene expression was assessed by RT-PCR. Results: The survival rate of cells treated by conditioned medium and serum for 24 and 48 h was significantly decreased as compared to control. Meanwhile, there was a significant increase in the survival rate of MCF-7 cells cultured with rosemary 50 and 100 μg / ml containing serum for 48 h, compared to group treated with conditioned medium and serum. A significant increase in P53, AIF and Bax gene expression, and also a significant decrease in Bcl-2 gene expression were observed in cells treated with conditioned medium and serum for 24 and 48h, as compared to the control. Rosemary at the concentration of 100 µg/ml and serum for 48 h significantly decreased P53, AIF and Bcl-2 genes and rosemary at concentration of 50 µg/ml containing serum for 24 and 48 h significantly decreased Bax gene expression compared to conditioned medium and serum group. Conclusion: The AIF-dependent apoptotic pathway was activated in MCF-7 cells after treatment with conditioned medium 24 and 48 h and rosemary 100 containing serum after 48 h. [ABSTRACT FROM AUTHOR]

Introduction: Breast cancer cells produce exosomes that promote tumorigenesis. The anticancer properties of gallic acid have been reported. However, the mechanism underlying its anticancer effect on the exosomal secretory pathway is still unclear. We investigated the effect of gallic acid on exosome biogenesis in breast cancer cell lines. Methods: The cytotoxic effect of gallic acid on MCF-10a, MCF-7, and MDA-MD-231 cells was measured by MTT assay after 48 hours treatment. Expression of miRNAs including miRNA-21, -155, and 182 as well as exosomal genes such as Rab27a, b, Rab11, Alix, and CD63; along with HSP-70 (autophagy gene), was determined using Q-PCR. The subcellular distribution of it was monitored by flow cytometry analysis. Isolated exosomes were characterized by transmission and scanning electron microscopes and flow cytometry. Acetylcholinesterase activity is used to measure the number of exosomes in supernatants. In addition, autophagy markers including LC3 and P62 were measured by ELISA. Results: Data showed that gallic acid was cytotoxic to cells (P < 0.05). Gallic acid modulated expression of miRNAs and down-regulated transcript levels of exosomal genes and up-regulated the HSP-70 gene in three cell lines (P < 0.05). The surface CD63/total CD63 ratio as well as acetylcholinesterase activity decreased in treated cells (P < 0.05). The protein level of LC3 was increased in three cell lines, while the expression of P62 increased in MCF-7 and MDA-MB-231 cancer cell lines. Conclusion: Together, gallic acid decreased the activity of the exosomal secretory pathway in breast cancer cell lines, providing evidence for its anti-cancer effects. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the safety and potential use of soy isoflavones in the treatment of skin problems, difficult-to-heal wounds and postoperative scars in women after the oncological treatment of breast cancer. The effects of different concentrations of genistein as a representative of soy isoflavonoids on MCF-7 tumor cells and BJ skin fibroblasts cultured in vitro were assessed. Genistein affects both healthy dermal BJ fibroblasts and cancerous MCF-7 cells. The effect of the tested isoflavonoid is closely related to its concentration. High concentrations of genistein destroy MCF-7 cancer cells, regardless of the exposure time, with a much greater effect on reducing cancer cell numbers at longer times (48 h). Lower concentrations of genistein (10 and 20 μM) increase the abundance of dermal fibroblasts. However, higher concentrations of genistein (50 μM and higher) are detrimental to fibroblasts at longer exposure times (48 h). Our studies indicate that although genistein shows high potential for use in the treatment of skin problems, wounds and surgical scars in women during and after breast cancer treatment, it is not completely safe. Introducing isoflavonoids to treatment requires further research into their mechanisms of action at the molecular level, taking into account genetic and immunological aspects. It is also necessary to conduct research in in vivo models, which will allow for eliminating adverse side effects of therapy. [ABSTRACT FROM AUTHOR]

Plant secondary metabolites and their derivatives play a significant role in anticancer drug therapy since they are effective against specific characteristics while reducing side effects. Dillapiole is a phenylpropanoid that holds several bioactivities like anti-fungal, anti-inflammatory, anti-leishmanial, and anti-cancer. This study aims to investigate the possible cytotoxic effect of dillapiole on human breast cancer, MCF-7 cells. Cells were cultured in complete RPMI media and incubated at standard culture conditions. After the cells reached 80% confluency, cells were treated with various concentrations (ranging from 0 μM to 150 μM) of dillapiole and tamoxifen as a positive control. Cells were later incubated at 48 and 72 h. Using WST-1 assay, the cytotoxic effect was determined for both incubation times. Results show tamoxifen inhibited the MCF-7 cells with the IC50 at 75.9 μM and 39.8 μM for 48 and 72 h respectively. Parallel with the positive control results, there was a significant cytotoxic effect of dillapiole against MCF-7 cells at 48- and 72-hr incubation with the IC50 at 92.1 μM and 63.1 μM respectively. Based on these results, dillapiole was cytotoxic against MCF-7 cells and its cytotoxic activity was both in a time and dosedependent manner (<0.05). The morphological analysis supported the WST-1 assay. Our preliminary finding is in agreement with other previous studies, suggesting that dillapiole appears to be a promising anti-cancer agent and opens a wider possibility of downstream analysis on its underlying cytotoxicity mechanism. [ABSTRACT FROM AUTHOR]

Hypoxia-inducible factor-1α (HIF-1α) is a major transcriptional regulator that plays a crucial role in the hypoxic response of rapidly growing tumors. Overexpression of HIF-1α has been associated with breast cancer metastasis and poor clinical prognosis. Plumbagin, the main phytochemical from Plumbago indica, exerts anticancer effects via multiple mechanisms. However, its precise mechanisms on breast cancer cells under hypoxic conditions has never been investigated. This study aims to examine the anticancer effect of plumbagin on MCF-7 cell viability, transcriptional activity, and protein expression of HIF-1α under normoxia and hypoxia-mimicking conditions, as well as reveal the underlying signaling pathways. The results demonstrate that plumbagin decreased MCF-7 cell viability under normoxic conditions, and a greater extent of reduction was observed upon exposure to hypoxic conditions induced by cobalt chloride (CoCl2). Mechanistically, MCF-7 cells upregulated the expression of HIF-1α protein, mRNA, and the VEGF target gene under CoCl2-induced hypoxia, which were abolished by plumbagin treatment. In addition, inhibition of HIF-1α and its downstream targets did not affect the signaling transduction of the PI3K/Akt/mTOR pathway under hypoxic state. This study provides mechanistic insight into the anticancer activity of plumbagin in breast cancer cells under hypoxic conditions by abolishing HIF-1α at transcription and post-translational modifications. [ABSTRACT FROM AUTHOR]

The purpose of this study was to evaluate the potential of a newly modified cyclodextrin derivative, water-soluble β-cyclodextrin–epichlorohydrin (β-CD), as an effective drug carrier to enhance the poor solubility and bioavailability of galangin (GAL), a poorly water-soluble model drug. In this regard, inclusion complexes of GAL/β-CDP were prepared. UV-VIS spectrophotometry, Fourier-transform infrared spectroscopy (FTIR), X-ray crystallography (XRD), zeta potential analysis, particle size analysis, field emission scanning electron microscopy (FESEM), and transmission electron microscopy (TEM) were applied to characterize the synthesized GAL/β-CD. Michigan Cancer Foundation-7 (MCF-7; human breast cancer cells) and rat embryo fibroblast (REF; normal cells) were employed to examine the in vitro cytotoxic effects of GAL/β-CD using various parameters. The dye-based tests of MTT and crystal violet clearly exhibited that GAL/β-CD-treated cells had a reduced proliferation rate, an influence that was not found in the normal cell line. The cells' death was found to follow apoptotic mechanisms, as revealed by the dye-based test of acridine orange/ethidium bromide (AO/EtBr), with the involvement of the mitochondria via caspase-3-mediated events, as manifested by the Rh 123 test. We also included a mouse model to examine possible in vivo toxic effects of GAL/β-CD. It appears that the inclusion complex does not have a significant influence on normal cells, as indicated by serum levels of kidney and liver enzymatic markers, as well as thymic and splenic mass indices. A similar conclusion was reached on the histological level, as manifested by the absence of pathological alterations in the liver, kidney, thymus, spleen, heart, and lung. [ABSTRACT FROM AUTHOR]

Rhodophyta (red algae) has been recognized as a rich source of natural compounds with a wide range of medicinal and biological properties, including anti-oxidants, anti-proliferative, anti-tumor, anti-viral, and anti-coagulant properties. The main goal of this study is to structurally characterize and assess cytotoxicity of both ethanolic and chloroform extracts of Sarconema filiforme and Laurencia obtusa red seaweed collected from the Suez Canal coasts, Egypt. Extracts of S. filiforme and L. obtusa were prepared and characterized using GC/MS analysis and MTT assay was used to examine their toxicity against human breast cancer (MCF-7 and MDA-MB-231 cells) and lung adenocarcinoma (A549 cells) cell lines. Using GC/MS analysis, a total of 34 and 29 different compounds were identified in the extracts of S. filiforme and L. obtusa, respectively. The identified components include alkanes, phenol derivative, benzoic acid esters, fatty acids, fatty acid esters, terpenes, fatty acyls, steroids, and prostaglandin. The most abundant constituents in both algae species are cholesterol and diisooctyl phthalate. The in vitro assays revealed a mild to moderate cytotoxicity of the two crude extracts of both species on MCF-7, MDA-MB-231, and A549 cells. Based on GC/MS analysis, it is obvious that S. filiforme and L. obtusa extracts contain various biologically active compounds with potential antimicrobial, antioxidant, antiviral, anti-inflammatory and antitumor activities. Further bioguided fractionations are recommended to identify and isolate antitumor active compounds of both extracts. [ABSTRACT FROM AUTHOR]

Anticancer activity of mononuclear Pt(II) complexes bearing organoselenide moiety. [Display omitted] • Syntheses and characterization of four new mononuclear Pt(II) complexes as efficient chemotherapeutic agents. • The complexes were synthesized from heterotridentate coordination core (NOSe) based Schiff bases. • The cytotoxicity of synthesized Pt(II) complexes were examined on MCF-7 and NIH-3T3 cell lines. • ROS generation, flow cytometery and Transwell assays were performed to determine the mechanism of anticancer action. This work features design and syntheses of four mononuclear Pt(II) complexes [Pt(L 1 –H)Cl]; 1, [Pt(L 2 –H)Cl]; 2, [Pt(L 3 –H)Cl]; 3, and [Pt(L 4 –H)Cl]; 4, which were judiciously prepared by tethering with a ONSe donor core of Schiff base ligands (L 1 –L 4). The complexes were fully characterized by IR, NMR spectra, elemental analysis and single crystal X-ray diffraction (sc-XRD) analysis. Notably, cytotoxicity profile of these structurally amended complexes against human breast cancer cell line (MCF-7) and mouse model fibroblast cells (NIH-3T3) cell lines revealed remarkable anticancer activity and selectivity based on their structural activity. [ABSTRACT FROM AUTHOR]

[Display omitted] • The study investigates and compare the photothermal properties of new type of carbon quantum dots with different shapes of gold nanostructures as well known photothermal agents. • Copper-doped carbon quantum dots were synthesized through a hydrothermal method, while gold nanoparticles (AuNPs) and gold nanorods (AuNRs) were synthesized using sodium sulfide reduction and growth methods, respectively. • The results show that carbon quantum dots can reach similar temperatures as gold nanostructures. • Photothermal conversion efficiencies of Cu-CQDs and gold nanostructures were calculated, and their photothermal cell death was examined on MCF-7 cancer cells. • Results showed that CQDs and AuNRs had higher photothermal conversion efficiencies compared to AuNPs, and all synthesized materials demonstrated photothermal therapeutic effect aginst MCF-7 cells.. This study focuses on the comparison of the photothermal (PT) properties of the new carbon quantum dots with two types of gold nanostructures including gold nanoparticles and gold nanorods.We prepared and characterized CQDs doped with copper from ascorbic acid precursor (Cu-aCQDs) with 3 nm diameter and citric acid precursor (Cu-cCQDs) with 5 nm diameter by hydrothermal method, Gold nanoparticles (GNP) were synthesized using sodium sulfide reduction and Gold nanorods (GNR) (aspect ratio of 5) by growth methods. UV–Vis spectrophotometry, spectrofluorimetry, dynamic light scattering (DLS), and transmission electron microscopy (TEM) were used to analyze the optical and morphological properties of the nanoparticles. The fluorescence quantum yields of 2.14 % and 1.55 % were obtained for Cu-aCQDs and Cu-cCQDs respectively. The photothermal conversion efficiencies of 44 %, 66 %, 42 % and 57 % were obtained for Cu-aCQDs, Cu-cCQDs, GNPs and GNRs respectively. We also evaluated the toxicity and the photothermal therapy (PTT) performance of the nanoparticles on MCF-7 breast cancer cells. The ratio of the cell death (from photothermal agent) in the presence of LASER irradiation to its absence for Cu-aCQDs, Cu-cCQDs, GNPS and gold nanorods were 2.5, 5.3, 1.75 and 1.9 respectively. The CQDs had very low toxicity in the absence of LASER irradiation and only 15 % toxicity was obtained for 14.0 mg/mL of Cu-aCQDs and Cu-cCQDs, 350 μg/mL of GNPs and 87.5 of μg/mL gold nano rods. These results indicate that CQDs are less harmful than gold nanostructures in the absence of LASER irradiation and more effective than gold nanostructures when LASER irradiation is applied. [ABSTRACT FROM AUTHOR]

Greener fabrication of nanostructures has received remarkable attention due to their sustainability, cost-effectiveness, simplicity, and eco-friendliness. Opuntia ficus-indica-derived mucilage has not been exposed well to fabricate nanostructures. Thus, in this present investigation, we successfully synthesized tungsten trioxide (WO3) nanostructures using Opuntia ficus-indica-derived mucilage as bio-templates because it is more economical and environmentally friendly. Also, the fabricated WO3 nanostructures cytotoxic features and their photothermal effects were studied. The WO3 nanostructures were investigated using diverse analytical instruments: X-ray diffractometer (XRD), scanning electron microscope and, transmission electron microscope. Based on the structural and morphological characteristics of the WO3 nanostructures, they have sphere-like morphologies with diameters of 100 - 200 nm. As revealed by XRD, monoclinic crystalline WO3 nanostructures were formed. In vitro assays were used to assess the effect of WO3 nanostructures on cell viability and morphological features of cells. Based on in vitro assays, fabricated WO3 nanostructures showed slightly toxic behaviour in a human breast cancer cell line (MCF-7 cells). In contrast, after exposure to NIR lasers, the viability of WO3 nanostructures treated cells decreased significantly. Because the WO3 nanostructures have an excellent photothermal effect, which triggers cell death in cancer cells. Thus, the fabricated WO3 nanostructures can be used as a photothermal agent for cancer therapyGraphical Abstract: Greener fabrication of nanostructures has received remarkable attention due to their sustainability, cost-effectiveness, simplicity, and eco-friendliness. Opuntia ficus-indica-derived mucilage has not been exposed well to fabricate nanostructures. Thus, in this present investigation, we successfully synthesized tungsten trioxide (WO3) nanostructures using Opuntia ficus-indica-derived mucilage as bio-templates because it is more economical and environmentally friendly. Also, the fabricated WO3 nanostructures cytotoxic features and their photothermal effects were studied. The WO3 nanostructures were investigated using diverse analytical instruments: X-ray diffractometer (XRD), scanning electron microscope and, transmission electron microscope. Based on the structural and morphological characteristics of the WO3 nanostructures, they have sphere-like morphologies with diameters of 100 - 200 nm. As revealed by XRD, monoclinic crystalline WO3 nanostructures were formed. In vitro assays were used to assess the effect of WO3 nanostructures on cell viability and morphological features of cells. Based on in vitro assays, fabricated WO3 nanostructures showed slightly toxic behaviour in a human breast cancer cell line (MCF-7 cells). In contrast, after exposure to NIR lasers, the viability of WO3 nanostructures treated cells decreased significantly. Because the WO3 nanostructures have an excellent photothermal effect, which triggers cell death in cancer cells. Thus, the fabricated WO3 nanostructures can be used as a photothermal agent for cancer therapy [ABSTRACT FROM AUTHOR]

Background: Breast cancer (BC) is the leading cause of death worldwide. The severity of BC strictly depends on the molecular subtype. The less aggressive hormone-positive subtype is treated with adjuvant endocrine therapy (AET), which causes both physical and psychological side effects. This condition strongly impacts the adherence and persistence of AET among oncologic patients. Moreover, viral infections also constitute a serious problem for public health. Despite their efficacy, antiviral agents present several therapeutic limits. Accordingly, in the present work, we investigated the antitumor and antiviral activities of Orobanche crenata Forssk. (O. crenata), a parasitic plant, endemic to the Mediterranean basin, traditionally known for its beneficial properties for human health. Methods: The MTT assay was carried out to evaluate the cytotoxic effect of O. crenata leaf extract (OCLE) on human breast cancer cells (MCF-7 and MDA-MB-231) and the primary HFF-1 cell line. The lactic dehydrogenase (LDH) assay was performed on MCF-7 cells to analyze necrotic cell death. The antioxidant effect of OCLE was evaluated by intracellular determination of the reactive oxygen species and thiol groups, by DPPH and ABTS assays. The antiviral activity of OCLE was determined against Poliovirus 1, Echovirus 9, Human respiratory syncytial virus, Adenovirus type 2 and type 5, Coxsackievirus B1 (CoxB1) and B3 (CoxB3), Herpes simplex type 1 (HSV-1) and type 2 (HSV-2), and β-Coronavirus by the plaque reduction assay. Results: The extract, after 24 h of incubation, did not affect MDA-MB-231 and HFF-1 cell viability. However, at the same time point, it showed a dose-dependent inhibitory effect on MCF-7 cells, with an increase in LDH release. OCLE exhibited free radical scavenging activity and significantly increased non-protein thiol levels in MCF-7 cells. OCLE effectively inhibited HSV-1, HSV-2, CoxB1, and CoxB3 replication. Conclusions: The overall results showed an interesting inhibitory effect of OCLE on both MCF-7 cell survival and viral replication. [ABSTRACT FROM AUTHOR]

Background: Menopausal hormone therapy (MHT) is recommended for only five years to treat vasomotor symptoms and vulvovaginal atrophy because of safety concerns with long-term treatment. We investigated the ability of 2′,3′,4′-trihydroxychalcone (2′,3′,4′-THC) to modulate estrogen receptor (ER)-mediated responses in order to find drug candidates that could potentially prevent the adverse effects of long-term MHT treatment. Methods: Transfection assays, real time-polymerase chain reaction, and microarrays were used to evaluate the effects of 2′,3′,4′-THC on gene regulation. Radioligand binding studies were used to determine if 2′,3′,4′-THC binds to ERα. Cell proliferation was examined in MCF-7 breast cancer cells by using growth curves and flow cytometry. Western blots were used to determine if 2′,3′,4′-THC alters the E2 activation of the MAPK pathway and degradation of ERα. Chromatin immunoprecipitation was used to measure ERα binding to genes. Results: The 2′,3′,4′-THC/E2 combination produced a synergistic activation with ERα on reporter and endogenous genes in human U2OS osteosarcoma cells. Microarrays identified 824 genes that we termed reprogrammed genes because they were not regulated in U2OS-ERα cells unless they were treated with 2′,3′,4′-THC and E2 at the same time. 2′,3′,4′-THC blocked the proliferation of MCF-7 cells by preventing the E2-induced activation of MAPK and c-MYC transcription. The antiproliferative mechanism of 2′,3′,4′-THC differs from selective estrogen receptor modulators (SERMs) because 2′,3′,4′-THC did not bind to the E2 binding site in ERα like SERMs. Conclusion: Our study suggests that 2′,3′,4′-THC may represent a new class of ERα modulators that do not act as a direct agonists or antagonists. We consider 2′,3′,4′-THC to be a reprogramming compound, since it alters the activity of ERα on gene regulation and cell proliferation without competing with E2 for binding to ERα. The addition of a reprogramming drug to estrogens in MHT may offer a new strategy to overcome the adverse proliferative effects of estrogen in MHT by reprogramming ERα as opposed to an antagonist mechanism that involves blocking the binding of estrogen to ERα. [ABSTRACT FROM AUTHOR]

In this study, we investigated two formulations of chitosan-Pluronic P123 with different folate ligand designation for targeted delivery of Paclitaxel (PTX), in which folic acid (FA) was directly conjugated to chitosan (FA-Cs-P123) or substituted onto P123 (Cs-P123-FA). The results showed that the FA content of Cs-P123-FA was determined at 0.71 wt/wt% which was significantly higher than that of FA-Cs-P123 (0.31 wt/wt%). Two copolymers were low critical gel concentrations (CGC). FA-Cs-P123 and Cs-P123-FA nanogels performed high PTX encapsulation efficiency reaching 95.57 ± 5.51 and 92.51 ± 6.68 wt/wt%, respectively. Transmission electron microscopy (TEM) and zeta potential analysis indicated that the PTX-loaded nanogels were spherically formed around 60 nm in diameter along with positive charge. Furthermore, the PTX release profile was slow and it was controlled by the pH of the medium. In particular, in vitro biocompatibility assays indicated that both FA-Cs-P123 and Cs-P123-FA exhibited good biological compatibility with a human foreskin fibroblast cell line and well uptake efficiency into MCF-7 cancer cells. Cs-P123-FA nanogel significantly enhanced the cytotoxicity of PTX in comparison with FA-Cs-P123. The result indicates that Cs-P123-FA nanogels with a higher decorated FA content perform a better targeting efficiency; therefore, they could have great potential application towards breast cancer treatment. [ABSTRACT FROM AUTHOR]

This study was aimed to evaluate the impact of water-soluble β-cyclodextrin polymer (β-CDP), as a nanocarrier, on the therapeutic efficacy of the commercial doxorubicin (DOX). The β-CDP was synthesized by cross-linking of β-CD using epichlorohydrin. The chemical structure of the cross-linked β-CDP was verified by NMR and thermogravimetric analysis. The solubility of β-CDP in water was around 880 g in 1000 mL. Next, the DOX/β-CDP was formulated by the addition of the polymer into the various concentrations of DOX in a weight ratio of 1:10 and 1:20 (DOX: β-CDP). The formation of the inclusion complex of DOX with β-CDP was studied by UV–Vis spectroscopy. The UV–Vis spectra of DOX/β-CDP formulations show the appearance of the absorption peak at 480 nm and a significant decrease in the absorbance intensity of DOX signal compared to DOX solution. This verified the formation of the DOX/β-CDP complex and also the presence of free DOX in the DOX/β-CDP formulation. The hydrodynamic size of DOX/β-CDP formulation was obtained in the range of nanometer, and the complexion of DOX by β-CDP leads to a negative shift in the zeta potential. In vitro release profile shows a burst release followed by sustained release of DOX from DOX/β-CDP formulation. This is due to the presence of both free and encapsulated DOX. The cytotoxic effect of DOX solution and DOX/β-CDP formulation was evaluated by MTT assay against breast cancer (MCF-7) cell line. The anticancer activity of the DOX/β-CDP was higher than the DOX. [ABSTRACT FROM AUTHOR]

• Cytarabine loaded folate conjugated chitosan nanoparticles were prepared by ionic gelation method. • Positive zeta potential of synthesised FCCNPs indicates a stable nanoformulation. • Cell uptake of FCCNPs was tracked with the aid of fluorophore, Squaraine 650. • Treatment with FCCNPs upregulates genes, bax, cyt c and cas 9 involved in apoptosis. • Folate conjugated chitosan nanoparticles showed improved cytotoxicity of anticancer drug, cytarabine in MCF-7 cell lines. Anticancer drug cytarabine, has been widely used for treating haematological malignancies while it has minimal activity against solid tumours, which demands continuous infusion leading to high dose cytarabine toxicity. In this study, folate conjugated chitosan nanoparticles (FCCNP) were used for targeted delivery of cytarabine in breast adenocarcinoma cell lines by making use of the overexpressed folate receptors on the surface of MCF-7. Folate was conjugated to chitosan using carbodiimide. FCCNPs show spherical morphology with a size of<50 nm. Zeta potential of + 45.2 mV and PDI of 0.98 from DLS measurement confirms a stable monodisperse nanoformulation. Cytotoxicity was studied in folate receptor positive, MCF-7 and folate receptor negative, A-549 cell lines. Increased cellular uptake of the drug incorporated nanoparticles was confirmed in MCF-7 cells with fluorophore, squaraine 650 compared to A-549 cells. The relative fold of expression of genes involved in apoptosis such as bax, cyt c and cas 9 were upregulated. The present in vitro study confirms improved cytotoxicity of cytarabine folate conjugated chitosan nanoparticles in MCF-7 cells. [ABSTRACT FROM AUTHOR]

Introduction: Cancer is a non-communicable disease with over 18.1 million new cases and 9.6 million deaths annually according to WHO. Breast cancer is the number two highest count type of cancer trailing behind lung cancer. Treating cancer is expensive and have various side effects. Active components found in plants or fungi that have antioxidant and cytotoxic activity towards cancer cells, could be an alternative for anticancer. One of the fungi that is potentially developed as an anticancer, are the genus of Auricularia sp. also known as black-white fungus. This study aims to determine the phytochemicals components, antioxidant activity and cytotoxic effect of the Auricularia sp. towards MCF-7 breast cancer cells. Methods: Dried black-white fungus of Auricularia sp. grinded into a fine powder. Then, multilevel maceration is done with the n-hexane, ethyl acetate, ethanol as solvents. The extracts of black-white fungus undergo phytochemical screening and thin layer chromatography (TLC), followed by measuring antioxidant and evaluating the cytotoxic activity towards MCF-7 breast cancer cells. Results: black-white fungus of Auricularia sp. contained secondary metabolites of flavonoids, alkaloids, and triterpenoids and a total of 17 other phytochemical components. Ethyl acetate extract of black-white fungus showed a weak antioxidant activity towards DPPH free radical with IC50 of 215.51 µg/mL and a very active cytotoxic activity on MCF-7 cells with IC50 of 0.21 µg/mL. On the other hand, ethanol and n-hexane extracts of black-white fungus are categorized with an active cytotoxic activity on MCF-7 cells with IC50 of 29.28 µg/mL and 50.39 µg/mL, respectively. Conclusion: Black-white fungus Auricularia sp. that had anticancer activity towards breast MCF-7 cells should be considered as an alternative treatment for breast cancer therapy. [ABSTRACT FROM AUTHOR]

The study aimed to evaluate the possibility to perform electrochemotherapy using nanosecond pulsed electric field (nsPEF) and low electric field (LEF) monopolar electrical impulses to alleviate the problems of conventional electroporation. Two types of pulses have been used to treat MCF-7 human breast carcinoma cell line: very low voltage (electric field strength) long trains of short unipolar electric pulses, and low frequencies of extremely intense (40kV/cm), ultra-short (10ns) electric pulses. The electropermeabilization efficiency of the formed endocytotic vesicles was measured using the cloning efficacy test. The cell viability was decreased significantly at a repetition frequency begins from 0.01 Hz by ~35% and reached complete cell loss at 1 Hz of nanosecond pulses for cells treated before with monopolar pulses at 20 V/cm in the presence of BLM with 4 µM concentration. The uptake of non-permeant drugs has been done without plasma membrane permeabilization (classical electroporation), but by endocytosis. Nanosecond electric pulses can disrupt the membrane of endocytotic vesicles and release the cytotoxic drug bleomycin. [ABSTRACT FROM AUTHOR]