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Amberboa ramosa Roxb. (Asteraceae), commonly known as "Badaward", has been used for the treatment of tumors from ancient times. In this study, we aimed to scientifically authenticate the use of A. ramosa for breast cancer treatment. The whole plant fractions of A. ramosa were evaluated for their cytotoxic properties against MDA-MB-231 breast cancer cell lines. Among these fractions, Pet. ether, ethyl acetate, and ethanolic fractions exhibited considerable levels of cytotoxicity against MDA-MB-231 cells with IC 5 0 values of 78.55, 90.60, and 92.92 μ g/mL, respectively. The cell migration significantly decreased in ethyl acetate and ethanolic fractions. GC–MS was used to analyze the phytochemical profile of bioactive fractions, which revealed the presence of long-chain hydrocarbons, carboxylic acids, esters, alcohols, and terpenoids. Subsequently, the 96 compounds present in bioactive fractions were efficiently docked with EGFR and microtubule protein to evaluate affinity towards the targets. Eight common compounds were achieved using a docking-based approach against both target proteins, which showed similar interaction patterns as the reference inhibitors (colchicine and erlotinib). The key interactions revealed the potential of screened compounds as promising hits. 2-[1,2-Dihydroxyethyl]-9-[ α -d-ribofuranosyl]hypoxanthine showed the best dock score of −9.337 and −8.548 kcal/mol against EGFR and microtubule, respectively. 5-Oxo-cystofuranoquinol exhibited better dock score as well as binding energy against both targets. Chemical features present in the 08 dual inhibitors were also matched from the present EGFR and microtubule inhibitors for comparing the anticancer potential. Thus, this research revealed many new directions for developing natural lead compounds from Amberboa ramosa as dual inhibitors for treating breast cancer. GCMS-based phytochemical profiling and in-vitro anticancer activity were performed on the fractions of A. ramosa whole plant extract. Further, in silico assessment of the phytoconstituents from the top fraction highlighted their potential as EGFR and microtubule inhibitors. [ABSTRACT FROM AUTHOR]

Aim: Metal nanoclusters are emerging nanomaterials applicable for drug delivery. Here, the toxicity and oxidative stress induction of divalent cationic cadmium (Cd2+) was compared with a Cd in the form of nanocluster. Then, it was used for targeted drug delivery into breast cancer cell lines. Methods: Using a green chemistry route, a Cd nanocluster (Cd-NC) was synthesized based on bovine serum albumin. After characterization, its genotoxicity and oxidative stress induction were studied in both in vitro and in vivo. After that, it was conjugated with hyaluronic acid (HA). The efficiency of hyaloronized-Cd-CN (HA-Cd-NC) for loading and releasing crocin (Cro), an anticancer phytochemical, was studied. Finally, it was applied for cell death induction in a panel of breast cancer cell lines. Results: The comet assay results indicated that, unlike Cd2+ and potassium permanganate (KMnO4), no genotoxicity and oxidative stress was induced by Cd-NC in vitro. Then, the pharmacokinetics of this Cd-NC was studied in vivo. The data showed that Cd-NC has accumulated in the liver and excreted from the feces of mice. Unlike Cd2+, no toxicity and oxidative stress were induced by this Cd-NC in animal tissues. Then, the Cd-NC was targeted toward breast cancer cells by adding HA, a ligand for the CD44 cell surface receptor. After that, Cro was loaded on HA-Cd-NC and it was used for the treatment of a panel of human breast cancer cell lines with varying degrees of CD44. The half-maximal drug inhibitory concentration (IC50) of Cro was significantly decreased when it was loaded on HA-Cd-NC, especially in MDA-MB-468 with a higher degree of CD44 at the surface. These results indicate the higher toxicity of Cro toward breast cancers when carried out by HA-Cd-NC. Conclusions: The Cd-NC was completely safe and is a promising candidate for delivering anticancer drugs/phytochemicals into the targeted breast tumors.

Chest X-rays are used to assess diagnostic conditions for patients with breast cancer. The aim of this research was to study the radiation dose from chest X-ray on the response of breast cancer cells. In this research, the proliferation and cell numbers of the MDA-MB-231 cell line were studied at 1, 24, 48, 72 and 96 h after 0.42–0.82 mGy of chest X-ray irradiation. The results showed that the cell morphology of breast cancer cells did not change after irradiation. In contrast, it was found that the radiation dose from chest X-ray inhibited cell growth and the cell viability of MDA-MB-231. It can be seen that the changes at the cellular level occur within cancer cells from low-dose radiation. [ABSTRACT FROM AUTHOR]

Obstacles to the successful treatment of breast cancer patients with chemotherapeutic agents can be overcome with effective new strategies. It is still unclear how folic acid affects the onset and spread of breast cancer. The purpose of this study was to determine how folic acid affected the apoptotic and autophagic pathways of the breast cancer cell lines MCF‐7 and MDA‐MB‐231. In the present study, folic acid was applied to MCF‐7 and MDA‐MB‐231 breast cancer cell lines at different concentrations and for different durations. MTT analysis was used to investigate cytotoxic activity. All groups underwent the Tunel staining procedure to identify apoptosis and the immunofluorescence staining approach to identify the autophagic pathway. 24‐hour folic acid values were accepted as the most appropriate cytotoxic dose. In MCF‐7, cell cycle arrest was observed in the S phase and MDA‐MB‐231 G1/G0 phases. When apoptotic TUNEL staining was evaluated in both cell lines, folic acid significantly increased apoptosis. While a significant difference was observed between the groups in terms of Beclin 1 immunoreactivity in the MDA‐MB‐231 cell line, there was no significant difference in the MCF‐7 cell line. In addition, statistical significance was not observed LC3 immunoreactivity in both cell lines. In the study, it was observed that folic acid induced autophagy at the initial stage in the MDA‐MB‐231 cell line but had no inductive effect in the MCF‐7 cell line. In conclusion, our findings showed that folic acid has a potential cytotoxic and therapeutic effect on MCF‐7 and MDA‐MB‐231 breast cancer cell lines. [ABSTRACT FROM AUTHOR]

In this study, the cytotoxic and apoptotic effects of three phenolic compounds highly found in the poplar type propolis; pinostrobin (PS), pinocembrin (PC) and pinobanksin (PB), were investigated individually and in combination on hormon-positive (MCF-7) and triple negative (MDA-MB-231) breast cancer cell lines and fibrocystic breast epithelium (MCF-10A) as control. Assessment of cytotoxicity and apoptosis were performed with WST-1 and Annexin V-7AAD assays, respectively. All statistical analyses including the two-way ANOVA and multiple-t-test were performed using GraphPad Prism software. Individually, PB (P0.05). On MCF-7, the triple combination induced cytotoxic/apoptotic effects even with the 25% dose and 50% dose on MDA-MB-231(p

Objective(s): The present study evaluated the protein-based analysis to unravel the role and mechanism behind the Dendropthae falcata plant extract treatment in breast cancer cells. Materials and Methods: The protein sample was extracted from the cancer cells after treatment with the plant extract and subjected to two-dimensional electrophoresis for protein separation. Further, the proteins that were differentially regulated among the samples which were treated and non-treated were selected and processed further for protein identification using a tandem mass spectrometry approach.Results: Using these strategies, we identified 16 potential candidates which were showing remarkable changes in treated samples. All the candidates were analyzed further for gene ontology analysis, and it was observed that all proteins were involved in multiple pathways pertaining to the carcinogenesis process. Specifically, apoptotic pathway proteins including BAD, BIK, BID, CASP8, MCL1, BCL2, and BAK1 were highly impacted by treatment with D. falcata plant extract. All these protein hits were further taken for validation experiments using RT PCR analysis. Conclusion: Initiation of these apoptotic proteins by D. falcata plant extract treatment in breast cancer cells shows a positive direction toward nature-based alternative medicine.

In this study, the cytotoxic and apoptotic effects of three phenolic compounds highly found in the poplar type propolis; pinostrobin (PS), pinocembrin (PC) and pinobanksin (PB), were investigated individually and in combination on hormon-positive (MCF-7) and triple negative (MDA-MB-231) breast cancer cell lines and fibrocystic breast epithelium (MCF-10A) as control. Assessment of cytotoxicity and apoptosis were performed with WST-1 and Annexin V-7AAD assays, respectively. All statistical analyses including the two-way ANOVA and multiple-t-test were performed using GraphPad Prism software. Individually, PB (P<0.0001), PS (P<0.0001), and PC (P<0.05) demonstrated potent cytotoxic effects at moderate to high doses and late time intervals on MCF-7. PB and PS have been found to have a significant proliferative effect at low doses (P<0.0001), however, this effect disappeared in higher doses in this cell line. Dual combinations of PB+PC and PB+PS were toxic on MCF-10A, however, dual combination of PS+PC and the triple combination (PB+PS+PC) showed no cytotoxicity until high doses at late time intervals (P>0.05). On MCF-7, the triple combination induced cytotoxic/apoptotic effects even with the 25% dose and 50% dose on MDA-MB-231(p<0.0001). Our findings clearly showed that different combinations of these phenolic substances can have synergistic cytotoxic effects and even hormetic effects in non-tumorogenic cells. [ABSTRACT FROM AUTHOR]

Glutathione transferase Pi (GSTP1) expression is increased in many cancer types and is associated with multidrug resistance and apoptosis inhibition. Inhibitors of GSTP1-1 have the potential to overcome drug resistance and improve chemotherapy efficacy as adjuvant agents. This study investigated the effects of catechin and gossypol on human glutathione transferase Pi (GSTP1-1) activity and their cytotoxic effects on breast cancer cells (MCF-7) individually and in combination with tamoxifen (TAM). Gossypol effectively inhibited the enzyme with an IC50 value of 40 μM, compared to 200 μM for catechin. Gossypol showed stronger inhibition of GSTP1-1 activity (Ki = 63.3 ± 17.5 μM) compared to catechin (Ki = 220 ± 44 μM). Molecular docking analysis revealed their binding conformations to GSTP1-1, with gossypol binding at the subunit interface in an un-competitive manner and catechin showing mixed non-competitive inhibition. Gossypol had severe cytotoxic effects on both MCF-7 cells and normal BJ1 cells, while catechin had a weak cytotoxic effect on MCF-7 cells only. Combination therapy with TAM resulted in cytotoxicity of 27.3% and 35.2% when combined with catechin and gossypol, respectively. Gossypol showed higher toxicity to MCF-7 cells, but its strong effects on normal cells raised concerns about selectivity and potential side effects. [ABSTRACT FROM AUTHOR]

In the current study, the squid, Sepioteuthis lessoniana ink was used as a raw material. It summarizes physicochemical, elemental, and spectral properties (UV/Visible spectroscopy and FT-IR) of crude ink, whereas the biochemical analysis was performed with crude ink (CI) as well as melanin-free ink (MFI). The percentage yield was analyzed using various solvent extracts of CI and MFI. GC–MS was performed for the chemical constituents of the methanolic extract of ink. Furthermore, the methanolic extract was subjected to various biological applications. The physicochemical analysis defines the presence of moisture, ash, extractive value, solubility, and thermal stability of CI. The biochemical analysis reveals protein, lipid, and carbohydrate of 2.5, 2.2, and 2.37 mg/ml for CI and 2.8, 3.7, and 4.51 mg/ml for MFI respectively. The extract showed the highest zone of inhibition at 100 μg/ml. The antioxidant activity reveals the highest percentage of radical-scavenging activity in nitric oxide (NO) (89%), and total antioxidant capacity (TAC) assay showed the highest inhibition activity of 0.41 nm at 100 µg/ml. The cytotoxic ability of methanolic extract against MDA-MB-231 breast cancer cell line revealed an IC50 value of 10.13 μg/ml. Toxicity assay showed increased mortality of Artemia nauplii at higher concentrations (1000 ppm/40%) of extract. These findings indicate that S. lessoniana ink is a novel prospective product that needs to be characterized in order to increase its pharmacological activity. [ABSTRACT FROM AUTHOR]

In this study we presented a novel series of NNO tridentate ligands generating imino, amido and oxo donor pocket for Pd(II) coordination. All the compounds were meticulously characterized by elemental analysis and advanced spectroscopic techniques, including FTIR, proton and carbon NMR. The synthesized compounds underwent rigorous evaluation for their potential as anti-cancer agents, utilizing the aggressive breast cancer cell lines MDA-MB (ATCC) and MCF-7 as a crucial model for assessing growth inhibition in cancer cells. Remarkably, the MTT assay unveiled the robust anti-cancer activity for all palladium complexes against MDA-MB-231 and MCF-7 cells. Particularly, complex [Pd(L1)(CH3CN)] exhibited exceptional potency with an IC50 value of 25.50 ± 0.30 µM (MDA-MB-231) and 20.76 ± 0.30 µM (MCF-7), compared to respective 27.00 ± 0.80 µM and 24.10 ± 0.80 µM for cisplatin, underscoring its promising therapeutic potential. Furthermore, to elucidate the mechanistic basis for the anti-cancer effects, molecular docking studies on tyrosine kinases, an integral target in cancer research, were carried out. The outcome of these investigations further substantiated the remarkable anticancer properties inherent to these innovative compounds. This research offers a compelling perspective on the development of potent anti-cancer agents rooted in the synergy between ligands and Pd(II) complexes and presenting a promising avenue for future cancer therapy endeavors.

Objective(s): The present study evaluated the protein-based analysis to unravel the role and mechanism behind the Dendropthae falcata plant extract treatment in breast cancer cells. Materials and Methods: The protein sample was extracted from the cancer cells after treatment with the plant extract and subjected to two-dimensional electrophoresis for protein separation. Further, the proteins that were differentially regulated among the samples which were treated and non-treated were selected and processed further for protein identification using a tandem mass spectrometry approach. Results: Using these strategies, we identified 16 potential candidates which were showing remarkable changes in treated samples. All the candidates were analyzed further for gene ontology analysis, and it was observed that all proteins were involved in multiple pathways pertaining to the carcinogenesis process. Specifically, apoptotic pathway proteins including BAD, BIK, BID, CASP8, MCL1, BCL2, and BAK1 were highly impacted by treatment with D. falcata plant extract. All these protein hits were further taken for validation experiments using RT PCR analysis. Conclusion: Initiation of these apoptotic proteins by D. falcata plant extract treatment in breast cancer cells shows a positive direction toward nature-based alternative medicine. [ABSTRACT FROM AUTHOR]

Synthesis, characterization, and biological applications of zinc oxide nanoparticles using P. cristatus.

Estrogen receptor-positive breast cancers (ER+ BCas) are the most common form of BCa and are increasing in incidence, largely due to changes in reproductive practices in recent decades. Tamoxifen is prescribed as a component of standard-of-care endocrine therapy for the treatment and prevention of ER+ BCa. However, it is poorly tolerated, leading to low uptake of the drug in the preventative setting. Alternative therapies and preventatives for ER+ BCa are needed but development is hampered due to a paucity of syngeneic ER+ preclinical mouse models that allow pre-clinical experimentation in immunocompetent mice. Two ER-positive models, J110 and SSM3, have been reported in addition to other tumour models occasionally shown to express ER (for example 4T1.2, 67NR, EO771, D2.0R and D2A1). Here, we have assessed ER expression and protein levels in seven mouse mammary tumour cell lines and their corresponding tumours, in addition to their cellular composition, tamoxifen sensitivity and molecular phenotype. By immunohistochemical assessment, SSM3 and, to a lesser extent, 67NR cells are ER+. Using flow cytometry and transcript expression we show that SSM3 cells are luminal in nature, whilst D2.0R and J110 cells are stromal/basal. The remainder are also stromal/basal in nature; displaying a stromal or basal Epcam/CD49f FACS phenotype and stromal and basal gene expression signatures are overrepresented in their transcript profile. Consistent with a luminal identity for SSM3 cells, they also show sensitivity to tamoxifen in vitro and in vivo. In conclusion, the data indicate that the SSM3 syngeneic cell line is the only definitively ER+ mouse mammary tumour cell line widely available for pre-clinical research. [ABSTRACT FROM AUTHOR]

In the present research, oleuropein (OLE) contents from two Saudi Arabian wild olive trees (Olea europaea L.) leaves (O1 and O2), were collected from two nearby geographical sites differing in altitudes, and were determined via UHPLC-MS analysis. Moreover, total bioactive contents, antioxidant, and cytotoxicity (against MCF-7 and MDA-MB-231 cells) potential were also evaluated. The sample (O2) was found to contain significantly (p < 0.05) higher OLE content (4.13 ± 1.0 mg/g DW) compared with the sample (O1) having OLE content (3.63 ± 1.1 mg/g DW). A similar trend was observed regarding total bioactive contents and antioxidant potential. However, both samples exhibited low cytotoxicity against tested cell lines. Furthermore, with hierarchical cluster analysis that compared the results of our samples (O1 and O2) to other samples reported in the literature, it was found that the variance in OLE content and biological activities from Al Baha region leaves had a resemblance to other reported superior cultivars. [ABSTRACT FROM AUTHOR]

Introduction: Hydrogel nanoparticles, also known as nanogels (NGs), have been recently proposed as alternative supramolecular vehicles for the delivery of biologically relevant molecules like anticancer drugs and contrast agents. The inner compartment of peptide based NGs can be opportunely modified according to the chemical features of the cargo, thus improving its loading and release. A full understanding of the intracellular mechanism involved in nanogel uptake by cancer cells and tissues would further contribute to the potential diagnostic and clinical applications of these nanocarriers, allowing the fine tuning of their selectivity, potency, and activity. The structural characterization of nanogels were assessed by Dynamic Light Scattering (DLS) and Nanoparticles Tracking Analysis (NTA) analysis. Cells viability of Fmoc-FF nanogels was evaluated by MTT assay on six breast cancer cell lines at different incubation times (24, 48, and 72 h) and peptide concentrations (in the range 6.25 × 10−4 ÷ 5·10−3 × wt%). The cell cycle and mechanisms involved in Fmoc-FF nanogels intracellular uptake were evaluated using flow cytometry and confocal analysis, respectively. Fmoc-FF nanogels, endowed with a diameter of ~130 nm and a zeta potential of ~−20.0/−25.0 mV, enter cancer cells via caveolae, mostly those responsible for albumin uptake. The specificity of the machinery used by Fmoc-FF nanogels confers a selectivity toward cancer cell lines overexpressing the protein caveolin1 and efficiently performing caveolae-mediated endocytosis. [ABSTRACT FROM AUTHOR]

In vitro tumor models that are 3-dimensional (3D) have emerged as a significant area in the field of cancer research over the past several years. In order for breast cancer cell lines to grow and develop, it is important to select a scaffold, determine a strategy for seeding cells into the scaffold, then cultivate the cells under a variety of conditions. Therefore, we cultivated MCF-7 cells and fibroblasts on a gelatin-alginate scaffold alone or in co-culture under static or dynamic culture conditions in order to produce a 3D tumor model. MCF-7 and fibroblast were seeded into Gellatin-Alginate by Centrifugation and Incubation. After that, the cell proliferation was examined by MTT assay and the cell number determination in the scaffold. The morphology of MCF-7 was observed by H&E staining and SEM. The results showed that the co-culture of MCF-7 cells and fibroblasts in the scaffold exhibited an increase in cell mass size. Their mass morphologies feature a significant number of MCF-7 cells with a round structure that persists for an extended period of time. Perfusion bioreactors also demonstrate an increase in the size of cell mass (3 times higher than static culture). As a result, the long-term stability of the structure offers the possibility of cancer biology research and drug testing, especially the sustained release or actions experiements. [ABSTRACT FROM AUTHOR]

Introduction: Long non-coding RNAs play an important role in regulating gene expression, RNA processing, histone modification, and rearrangement of chromatin genes. These molecules can also be involved in many biological processes, such as organogenesis, cell differentiation, development, genome imprinting, quantitative compensation, and tumorigenesis. High expression of MALAT1 (a type of lncRNA) in many cancers, including breast cancer, indicates that a disorder of MALAT1 regulation is an important factor in the development of many types of cancer. Breast cancer is the most common cancer among women worldwide, and the invasion, as well as metastasis of this disease, are considered among the main causes of death. The present study aimed to knock out the MALAT1 gene in the MDA-MB-361 breast cancer cell line and evaluate its function and effects on the expression of genes associated with apoptosis. Material & Methods: In this study, two types of sgRNA were designed by CHOPCHOP software for exon 1 of the MALAT1 gene. These sgRNAs were cloned separately into two CRISPR vectors to generate the recombinant vectors PX459-sgRNA1 and PX459-sgRNA2. Co-transfection of these two recombinant vectors into the MDA-MB-361 cancer cell line was performed using lipofectamine 2000. MALAT1 gene editing was investigated in the cells receiving recombinant vectors. The expression of genes related to apoptosis was analyzed by Real-Time PCR. Cell proliferation and apoptosis were assessed by MTT and flow cytometry methods, respectively. (Ethic code: IR.IAU.M.REC.1399.010) Findings: The MALAT1 gene was edited by the CRISPR method in MDA-MB-361 cells. The rate of cell proliferation in the cells of the treatment group, compared to the control groups, showed a significant decrease (P

BACKGROUND: Breast cancer is the most fatal type of cancer in women worldwide. Many chemotherapeutics targeted breast cancer however, they have frightening side effects. One method of controlling cancer cell growth is targeting apoptosis. OBJECTIVE: This study aimed to induce apoptosis in breast cancer cells by purifying L-asparaginase from human breast milk Lactobacillus reuteri isolates via inhibition of Caspases 8 and 9. METHODS: The best L. reuteri isolates producing L-asparagine with the highest enzyme activity were identified from human breast milk and chosen for L-asparaginase purification. The MTT cell viability assay used for measure the toxicity of the enzyme. Breast cancer cell line was used to study the effect of the enzyme on the caspase 8 and caspase 9 gene expression. RESULTS: The MTT cell viability assay showed the inhibition rates ranged between 30% and 80%, of cell death, occurred when 3.125, 6.25, 12.5, 25, 50, and 100 μg/ml of the enzyme used and IC50 was 4.305 μg/ml. The breast cell lines were treated with the enzyme at a concentration of IC50 value. The Cas8 and Cas9 genes expression in L-asparagine treated breast cancer cell line at a concentration of IC50 value were upregulated (the fold of gene expression are 2.071 and 1.197 respectively). CONCLUSIONS: Breast milk L. reuteri L-asparaginase induces apoptosis via Cas8 and Cas9 upregulation in the breast cancer cell line. L. reuteri L-asparaginase treatment may be the hopeful approach for the management of breast cancer. Furthermore, the results may highlight the fact that the presence of L-asparaginase-producing L. reuteri isolates in human breast milk may aid in breast cancer improvement or even prevention. [ABSTRACT FROM AUTHOR]

A new series of isatin hybrids (5a–5g) were designed, synthesized, and characterized spectroscopically. The synthesized compounds were evaluated for their cytotoxic activity against human breast cancer cell line (MCF-7) by in vitro MTT assay. Amongst the tested compounds, 5e bearing benzyl moiety at N4 piperazine was found to be the most active with a promising IC50 value (12.47 μM). Moreover, the active compounds 5e and 5g were subjected to antitumor evaluation in vivo against Dalton's ascitic lymphoma (DAL) cell line and the results suggested that the most active compound 5e can normalize the blood picture in comparison to the standard drug. In-silico molecular docking study using the crystal structure of Hsp90 protein described the role of significant protein–ligand interactions and revealed more insights into the binding mode. The drug-likeliness of the compounds was predicted based on the Lipinski's rule of five and pharmacokinetic ADME parameters. Hence, the synthesized isatin hybrids can be used as new starting point anticancer lead compounds demonstrating drug-like properties, which can be explored further for anticancer drug discovery. [ABSTRACT FROM AUTHOR]

The goal of this work was to see how melatonin affected Bax and Bcl‐2 expression, as well as apoptosis and autophagy, in MCF‐7 and MDA‐MB‐231 breast cancer cell lines, which have distinct hormonal sensitivities. In this study, to investigate the IC50 value of melatonin, varied melatonin concentrations were administered to MCF‐7 and MDA‐MB‐231 breast cancer cell lines. Moreover, cytotoxic activities were analyzed through MTT analysis. Five subgroups were created for both cell lines: control, IC50‐MeL, hIC50‐MeL, DMSO1, and DMSO2. To evaluate the apoptotic effect of melatonin, immunofluorescence staining methods of TUNEL, Bax, and Bcl‐2 were used, and to examine the effects of autophagy, immunofluorescence staining methods of Beclin‐1, LC3, and p62 were used. In vitro results revealed upregulation of the expression of TUNEL and Bax in both MCF‐7 and MDA‐MB‐231 cell lines regarding dose and time, but downregulation of Bcl‐2 expression. Moreover, autophagy results were consistent with in vitro apoptosis results in both MCF‐7 and MDA‐MB‐231 cell lines. We determined that the expressions of the autophagy markers Beclin‐1, LC3, and p62 were increased. Our findings indicate that treatment of breast cancer cells with melatonin increased the inhibitory effect of melatonin on cell growth through both apoptosis and autophagy in vitro. Consequently, it was concluded that melatonin might adjust the expression balance of markers that have a role in cell death mechanisms and significantly promote these mechanisms. Therefore, melatonin can inhibit the growth of breast cancer cells by inducing cell death. [ABSTRACT FROM AUTHOR]

A series of novel fluorinated 1,5-benzothiazepine derivatives were synthesized, characterized and evaluated for in vitro anticancer and antibacterial activity. The in vitro anticancer activity of the synthesized compounds 4a–h was evaluated against four human cancer cell lines namely lung (A549), breast (MCF-7), liver (HEPG2) and prostate (PC-3). Compounds 4c, 4d, 4g and 4h exhibited good activity with GI50

The biomolecule-coated nanotitania catalysts were synthesised using rhizome extract of Gloriosa superba and the characteristics of the synthesised nanocatalysts were investigated by using various physiochemical methodologies. The antibacterial activity of the biomolecule coated nanotitania catalysts was tested against harmful microbial human pathogens. Nanotitania catalysts were found to be the most potential agent against gram negative bacterium i.e. Staphylococcus epidermidis. An efficient anti-biofilm activity was also observed against biofilm developing bacteria namely S. epidermidis and Pseudomonas aeruginosa. The 50% inhibitory concentration (IC50) of nanotitania catalysts noticed was 46.64 and 61.81 µg/mL for MCF-7 (cancer) L929 (normal) cell lines, respectively. Bioengineered nanotitania catalysts exhibited potential anticancer activity against breast cancer cell line. AO/EtBr staining results show distinct morphological variations such as orange and red coloured apoptotic bodies were identified in cancer cells that were treated with nanotitania catalysts. Further, the nuclear changes, mitochondrial depolarization and increased reactive oxygen species (ROS) level were also detected in nanotitania catalysts treated MCF-7 cells by Hoechst, rhodamine and DCFH-DA probe staining techniques. COMET assay confirmed the DNA destruction in the nanotitania treated cancer cells. In addition, the nanotitania catalysts exhibited potential photocatalytic activity against inorganic toxic dyes and the maximum rate of dye degradation was observed for crystal violet. The present results strongly suggest that the biomolecule coated nanotitania catalysts could be used as potential and novel compound towards biomedical as well as photocatalytic applications.

Abstract Cancer is the second most killer worldwide causing millions of people to lose their lives every year. In the case of women, breast cancer takes away the highest proportion of mortality rate than other cancers. Due to the mutation and resistance-building capacity of different breast cancer cell lines against conventional therapies, this death rate is on the verge of growth. New effective therapeutic compounds and treatment method is the best way to look out for in this critical time. For instance, new synthetic derivatives/ analogues synthesized from different compounds can be a ray of hope. Numerous synthetic compounds have been seen enhancing the apoptosis and autophagic pathway that directly exerts cytotoxicity towards different breast cancer cell lines. To cease the ever-growing resistance of multi-drug resistant cells against anti-breast cancer drugs (Doxorubicin, verapamil, tamoxifen) synthetic compounds may play a vital role by increasing effectivity, showing synergistic action. Many recent and previous studies have reported that synthetic derivatives hold potentials as an effective anti-breast cancer agent as they show great cytotoxicity towards cancer cells, thus can be used even vastly in the future in the field of breast cancer treatment. This review aims to identify the anti-breast cancer properties of several synthetic derivatives against different breast cancer and multi-drug-resistant breast cancer cell lines with their reported mechanism of action and effectivity.

Abstract The colony stimulating factor 2 receptor subunit beta (CSF2RB) is the common signaling subunit of the cytokine receptors for IL‐3, IL‐5, and GM‐CSF. Several studies have shown that spontaneous and random mutants of CSF2RB can lead to ligand independence in vitro. To date, no report(s) have been shown for the presence of potentially transforming and oncogenic CSF2RB mutation(s) clinically in cancer patients until the first reported case of a leukemia patient in 2016 harboring a germline‐activating mutation (R461C). We combined exome sequencing, pathway analyses, and functional assays to identify novel somatic mutations in KAIMRC1 cells and breast tumor specimen. The patient’s peripheral blood mononuclear cell (PBMC) exome served as a germline control in the identification of somatic mutations. Here, we report the discovery of a novel potentially transforming and oncogenic somatic mutation (S230I) in the CSF2RB gene of a breast cancer patient and the cell line, KAIMRC1 established from her breast tumor tissue. KAIMRC1 cells are immortalized and shown to survive and proliferate in ligand starvation condition. Immunoblot analysis showed that mutant CSF2RB signals through JAK2/STAT and PI3K/mTOR pathways in ligand starvation conditions. Screening a small molecule kinase inhibitor library revealed potent JAK2 inhibitors against KAIMRC1 cells. We, for the first time, identified a somatic, potentially transforming, and oncogenic CSF2RB mutation (S230I) in breast cancer patients that seem to be an actionable mutation leading to the development of new therapeutics for breast cancer.

Recent evidences from clinical trials (NCT04486911) revealed that the combination of pyrotinib, letrozole, and dalpiciclib exerted optimistic therapeutic effect in treating HER2+HR+ breast cancer; however, the underlying molecular mechanism remained elusive. Through the drug sensitivity test, the drug combination efficacy of pyrotinib, tamoxifen, and dalpiciclib to BT474 cells was tested. The underlying molecular mechanisms were investigated using immunofluorescence, Western blot analysis, immunohistochemical staining, and cell cycle analysis. Potential risk factor that may indicate the responsiveness to drug treatment in HER2+/HR+ breast cancer was identified using RNA-sequence and evaluated using immunohistochemical staining and in vivo drug susceptibility test. We found that pyrotinib combined with dalpiciclib exerted better cytotoxic efficacy than pyrotinib combined with tamoxifen in BT474 cells. Degradation of HER2 could enhance ER nuclear transportation, activating ER signaling pathway in BT474 cells, whereas dalpiciclib could partially abrogate this process. This may be the underlying mechanism by which combination of pyrotinib, tamoxifen, and dalpiciclib exerted best cytotoxic effect. Furthermore, CALML5 was revealed to be a risk factor in the treatment of HER2+/HR+ breast cancer and the usage of dalpiciclib might overcome the drug resistance to pyrotinib + tamoxifen due to CALML5 expression. Our study provided evidence that the usage of dalpiciclib in the treatment of HER2+/HR+ breast cancer could partially abrogate the estrogen signaling pathway activation caused by anti-HER2 therapy and revealed that CALML5 could serve as a risk factor in the treatment of HER2+/HR+ breast cancer.

Developing new anticancer agents are crucial for cancer treatment. Antiproliferative activity of L1H as a bis‐structured Schiff base was subjected to preliminary research in eight different kinds of cell lines by the cell viability method using different concentrations to determine their inhibitory concentration. L1H demonstrated the highest cytotoxicity in human breast cancer cell line MCF‐7. In this perspective, the MCF‐7 cell line was cultured for the examination of different molecular techniques, including MTT, apoptosis analysis by enzyme‐linked immunosorbent assay (ELISA), and comet assay. Moreover, the DNA ladder, acridine orange/ethidium bromide as another apoptotic cell analysis, markers of oxidative stress, and total antioxidant status, total thiol, and GSH as nonenzymatic antioxidants assay were conducted. The above techniques have proven that L1H is a growth inhibitor effect when compared to cisplatin as a positive control in human breast cancer cells, especially those affected by L1H. The findings clearly show that L1H evaluated in MCF‐7 cell lines causes rising or induced apoptosis, DNA damage, diminished antioxidant status against the increase of oxidized protein, and prevents cell proliferation. Manifold evidence supported our hypothesis that L1H has a potential therapeutically improved effect against the MCF‐7 cell line, and then without a doubt is a suitable candidate drug for investigating cancers next. Impact Statement: Breast cancer (BC) is one of the most common types of gynecologic cancer in females. It is considered to be the fourth leading death factor among other types of cancer. Despite new methods and drugs to treat BC and the good results received, we still have not scratched the surface of therapeutic cancer medications and there is a wide range of chemicals and natural products that have not yet been studied and tested as anticancer agents. The bis‐structured Schiff base [L1H] is considered a new compound with great anticancer potential. For the first time, apoptotic, cytotoxic, and genotoxic properties of the "bis‐structured Schiff" base were examined on breast cancer cell lines in different concentrations. An original study has been conducted by using standard apoptotic and cytotoxic tests such as single‐cell gel electrophoresis assay (comet assay), DNA fragmentation laddering, acridine orange test for DNA damage, and ELISA for apoptotic measuring. [ABSTRACT FROM AUTHOR]

Euphorbia resinifera latex has been extensively utilized in traditional medicine due to its range of bioactivities. Chromatographic separations on silica gel of ethanol extract of E. resinifera latex led to the development of a new procedure for isolating resiniferatoxin (4) via dried E. resinifera latex and the identification of nine compounds. Among these, catechol (7), protocatechuic acid (8) and 3,4-dihydroxyphenylacetic acid (9), known phenolic compounds, were identified for the first time in E. resinifera latex. Herein we investigated the effects of major compounds of the latex of E. resinifera on the yeast Saccharomyces cerevisiae, on the growth of Aspergillus carbonarius, a widespread fungal contaminant, and on the breast cancer cell line MCF7 as well as on MCF10A normal breast cells. 12-deoxyphorbol-13-isobutyrate-20-acetate (2) had an inhibiting effect on the growth of A. carbonarius, and 7-p-metoxyphenylacetate-3,8,12-triacetate ingol (3) showed a negative effect on yeast cell growth and also a cytotoxic effect on breast cancer cell line MCF7, but not on MCF10A cells. Deglucosyl euphorbioside A (5) and euphorbioside A (6) showed a discoloration effect that was possibly related to mitochondrial functionality in yeast, and also cytotoxicity only on the cancer cell line that was tested. Interestingly, treatment of MCF7 cells with 7-p-metoxyphenylacetate-3,8,12-triacetate ingol (3) and deglucosyl euphorbioside A (5) not only led to a specific cytotoxic effect but also to the increase in the level of intracellular ROS. [ABSTRACT FROM AUTHOR]

New estrone Schiff bases were designed and synthesized, and their structures and cytotoxicity were evaluated. Initial reagents estrone and 4'-bromomethyl-2-cyanobiphenyl react in the presence of potassium carbonate and potassium iodide in anhydrous acetone with 4'-(-3-yloxymethyl)-estrone-biphenyl-2-carbonitrile ether formation, which on sequential condensation with hydrazine hydrate and aromatic aldehydes gives steroidal Schiff bases in significant yield. Their structures were confirmed by elemental (C, H, N) analysis, mass spectroscopy, IR spectrophotometry, and 1H and 13C NMR spectrometry. The newly synthesized Schiff bases show cytotoxicity against MCF-7 breast cancer cell line with IC50 values on μM/mL level. [ABSTRACT FROM AUTHOR]

Introduction: Long non-coding RNAs play an important role in regulating gene expression, RNA processing, histone modification, and rearrangement of chromatin genes. These molecules can also be involved in many biological processes, such as organogenesis, cell differentiation, development, genome imprinting, quantitative compensation, and tumorigenesis. High expression of MALAT1 (a type of lncRNA) in many cancers, including breast cancer, indicates that a disorder of MALAT1 regulation is an important factor in the development of many types of cancer. Breast cancer is the most common cancer among women worldwide, and the invasion, as well as metastasis of this disease, are considered among the main causes of death. The present study aimed to knock out the MALAT1 gene in the MDA-MB-361 breast cancer cell line and evaluate its function and effects on the expression of genes associated with apoptosis. Material & Methods: In this study, two types of sgRNA were designed by CHOPCHOP software for exon 1 of the MALAT1 gene. These sgRNAs were cloned separately into two CRISPR vectors to generate the recombinant vectors PX459-sgRNA1 and PX459-sgRNA2. Co-transfection of these two recombinant vectors into the MDA-MB-361 cancer cell line was performed using lipofectamine 2000. MALAT1 gene editing was investigated in the cells receiving recombinant vectors. The expression of genes related to apoptosis was analyzed by Real-Time PCR. Cell proliferation and apoptosis were assessed by MTT and flow cytometry methods, respectively. (Ethic code: IR.IAU.M.REC.1399.010) Findings: The MALAT1 gene was edited by the CRISPR method in MDA-MB361 cells. The rate of cell proliferation in the cells of the treatment group, compared to the control groups, showed a significant decrease (P<0.05). Apoptosis levels were significantly increased in cancer cells the MALAT1 gene of which had been deleted. Moreover, the expression of BCL2 and survivin antiapoptotic genes in treated (edited) cells was significantly reduced, compared to control cells (P<0.05). Increased expression of proapoptotic genes P53, BAK, BAX, and FAS was also observed in the edited cells (P<0.05). Discussion & Conclusion: The results of this study confirm that the deletion of the MALAT1 gene has a significant effect on increasing apoptosis and reducing cell proliferation. A reduction in the expression of the MALAT1 gene can prevent the growth and proliferation of breast cancer cell lines. Therefore, it seems that the control of MALAT1 oncogene expression is useful and effective for controlling tumors. [ABSTRACT FROM AUTHOR]

Abstract Background MCF-7 breast cancer cell line is undoubtedly amongst the most extensively studied patient-derived research models, providing pivotal results that have over the decades translated to constantly improving patient care. Many research groups, have previously identified suitable reference genes for qPCR normalization in MCF-7 cell line. However, over the course of identification of suitable reference genes, a comparative analysis comprising these genes together in a single study has not been reported. Furthermore, the expression dynamics of these reference genes within sub-clones cultured over multiple passages (p) has attracted limited attention from research groups. Therefore, we investigated the expression dynamics of 12 previously suggested reference genes within two sub-clones (culture A1 and A2) cultured identically over multiple passages. Additionally, the effect of nutrient stress on reference gene expression was examined to postulate an evidence-based recommendation of the least variable reference genes that could be employed in future gene expression studies. Results The analysis revealed the presence of differential reference gene expression within the sub-clones of MCF-7. In culture A1, GAPDH-CCSER2 were identified as the least variable reference genes while for culture A2, GAPDH-RNA28S were identified. However, upon validation using genes of interest, both these pairs were found to be unsuitable control pairs. Normalization of AURKA and KRT19 with triplet pair GAPDH-CCSER2-PCBP1 yielded successful results. The triplet also proved its capability to handle variations arising from nutrient stress. Conclusions The variance in expression behavior amongst sub-clones highlights the potential need for exercising caution while selecting reference genes for MCF-7. GAPDH-CCSER2-PCBP1 triplet offers a reliable alternative to otherwise traditionally used internal controls for optimizing intra- and inter-assay gene expression differences. Furthermore, we suggest avoiding the use of ACTB, GAPDH and PGK1 as single internal controls.

Breast cancer is a well-known health issue that has been a major focus for healthcare professionals for quite some time. Still, the most common noninvasive diagnostic tool - mammography - results in a high false positive rate along with risks of exposure to radiation. These disadvantages are magnified and become more severe when screenings are done repeatedly. To tackle this problem, we introduce a novel framework for uncomplicated diagnosis of breast cancer. Our method utilizes the analytical technique of Mueller matrix decomposition and Stokes vector polarimetry from a polarized light system consisting of a helium-neon laser (wavelength of 632.5 nm), a quarter-wave plate, polarizers, and a Stokes polarimeter. Thus, this technique introduces no radiation. We extracted nine optical parameters of a breast cancer cell line - BT474 - and determined the relationship and separation power of these parameters to cancerous cells and healthy cells. Specifically, the samples were designed as a two-dimensional cellular model of malignant breast tumours that combined a range of four cell densities - 104, 105, 106, and 107 cells - per an area of 9 cm2. Nine optical parameters - orientation angle of linear birefringence (α), retardance or linear birefringence (β), optical rotation angle or circular birefringence (γ), orientation angle of linear dichroism (θd), linear dichroism (D), circular dichroism (R), degrees of linear depolarization (e1 and e2), and degree of circular depolarization (e3) - were extracted from a total of 40 samples using the polarized light system. The results revealed the positive correlations between three cell densities (104, 105, and 106) and the orientation angle of linear birefringence (R2 = 0.8038), linear birefringence (R2 = 0.8627), and linear dichroism (R2 = 0.9662). Meanwhile, both the orientation angle of linear dichroism and circular dichroism illustrated the negative correlation with that range of cell densities with R2 = 0.9983 and 0.9447, respectively. This proves that the optical parameters measured demonstrate significant association with the cells’ characteristics and thus, the proposed method could pave the way for an accessible diagnosis of breast cancer.

Introduction: Hydrogel nanoparticles, also known as nanogels (NGs), have been recently proposed as alternative supramolecular vehicles for the delivery of biologically relevant molecules like anticancer drugs and contrast agents. The inner compartment of peptide based NGs can be opportunely modified according to the chemical features of the cargo, thus improving its loading and release. A full understanding of the intracellular mechanism involved in nanogel uptake by cancer cells and tissues would further contribute to the potential diagnostic and clinical applications of these nanocarriers, allowing the fine tuning of their selectivity, potency, and activity. The structural characterization of nanogels were assessed by Dynamic Light Scattering (DLS) and Nanoparticles Tracking Analysis (NTA) analysis. Cells viability of Fmoc-FF nanogels was evaluated by MTT assay on six breast cancer cell lines at different incubation times (24, 48, and 72 h) and peptide concentrations (in the range 6.25 × 10−4 ÷ 5·10−3 × wt%). The cell cycle and mechanisms involved in Fmoc-FF nanogels intracellular uptake were evaluated using flow cytometry and confocal analysis, respectively. Fmoc-FF nanogels, endowed with a diameter of ~130 nm and a zeta potential of ~−20.0/−25.0 mV, enter cancer cells via caveolae, mostly those responsible for albumin uptake. The specificity of the machinery used by Fmoc-FF nanogels confers a selectivity toward cancer cell lines overexpressing the protein caveolin1 and efficiently performing caveolae-mediated endocytosis.

The biomolecule-coated nanotitania catalysts were synthesised using rhizome extract of Gloriosa superba and the characteristics of the synthesised nanocatalysts were investigated by using various physiochemical methodologies. The antibacterial activity of the biomolecule coated nanotitania catalysts was tested against harmful microbial human pathogens. Nanotitania catalysts were found to be the most potential agent against gram negative bacterium i.e. Staphylococcus epidermidis. An efficient anti-biofilm activity was also observed against biofilm developing bacteria namely S. epidermidis and Pseudomonas aeruginosa. The 50% inhibitory concentration (IC50) of nanotitania catalysts noticed was 46.64 and 61.81 µg/mL for MCF-7 (cancer) L929 (normal) cell lines, respectively. Bioengineered nanotitania catalysts exhibited potential anticancer activity against breast cancer cell line. AO/EtBr staining results show distinct morphological variations such as orange and red coloured apoptotic bodies were identified in cancer cells that were treated with nanotitania catalysts. Further, the nuclear changes, mitochondrial depolarization and increased reactive oxygen species (ROS) level were also detected in nanotitania catalysts treated MCF-7 cells by Hoechst, rhodamine and DCFH-DA probe staining techniques. COMET assay confirmed the DNA destruction in the nanotitania treated cancer cells. In addition, the nanotitania catalysts exhibited potential photocatalytic activity against inorganic toxic dyes and the maximum rate of dye degradation was observed for crystal violet. The present results strongly suggest that the biomolecule coated nanotitania catalysts could be used as potential and novel compound towards biomedical as well as photocatalytic applications. [ABSTRACT FROM AUTHOR]

Cancer is the second most killer worldwide causing millions of people to lose their lives every year. In the case of women, breast cancer takes away the highest proportion of mortality rate than other cancers. Due to the mutation and resistance-building capacity of different breast cancer cell lines against conventional therapies, this death rate is on the verge of growth. New effective therapeutic compounds and treatment method is the best way to look out for in this critical time. For instance, new synthetic derivatives/ analogues synthesized from different compounds can be a ray of hope. Numerous synthetic compounds have been seen enhancing the apoptosis and autophagic pathway that directly exerts cytotoxicity towards different breast cancer cell lines. To cease the ever-growing resistance of multi-drug resistant cells against anti-breast cancer drugs (Doxorubicin, verapamil, tamoxifen) synthetic compounds may play a vital role by increasing effectivity, showing synergistic action. Many recent and previous studies have reported that synthetic derivatives hold potentials as an effective anti-breast cancer agent as they show great cytotoxicity towards cancer cells, thus can be used even vastly in the future in the field of breast cancer treatment. This review aims to identify the anti-breast cancer properties of several synthetic derivatives against different breast cancer and multi-drug-resistant breast cancer cell lines with their reported mechanism of action and effectivity. [ABSTRACT FROM AUTHOR]

The colony stimulating factor 2 receptor subunit beta (CSF2RB) is the common signaling subunit of the cytokine receptors for IL‐3, IL‐5, and GM‐CSF. Several studies have shown that spontaneous and random mutants of CSF2RB can lead to ligand independence in vitro. To date, no report(s) have been shown for the presence of potentially transforming and oncogenic CSF2RB mutation(s) clinically in cancer patients until the first reported case of a leukemia patient in 2016 harboring a germline‐activating mutation (R461C). We combined exome sequencing, pathway analyses, and functional assays to identify novel somatic mutations in KAIMRC1 cells and breast tumor specimen. The patient's peripheral blood mononuclear cell (PBMC) exome served as a germline control in the identification of somatic mutations. Here, we report the discovery of a novel potentially transforming and oncogenic somatic mutation (S230I) in the CSF2RB gene of a breast cancer patient and the cell line, KAIMRC1 established from her breast tumor tissue. KAIMRC1 cells are immortalized and shown to survive and proliferate in ligand starvation condition. Immunoblot analysis showed that mutant CSF2RB signals through JAK2/STAT and PI3K/mTOR pathways in ligand starvation conditions. Screening a small molecule kinase inhibitor library revealed potent JAK2 inhibitors against KAIMRC1 cells. We, for the first time, identified a somatic, potentially transforming, and oncogenic CSF2RB mutation (S230I) in breast cancer patients that seem to be an actionable mutation leading to the development of new therapeutics for breast cancer. [ABSTRACT FROM AUTHOR]

Background: Cancer cell metastasis is facilitated by matrix-metalloproteinases through degradation of extracellular matrix (ECM) proteins and is a major cause of mortality. One of the most common remedies for cancer is chemotherapy, which has many side effects. Therefore, it seems necessary to find a way to reduce the side effects of these drugs while maintaining their anticancer effects. Quercetin (que) is a natural substance that has been reported to have anticancer activities. Objectives: This study aims at evaluating the effect of que in combination with doxorubicin (dox) on the migration of the MDA-MB-231 breast cancer cell line. Methods: The effects of que and dox on cell viability in 24h and 48 h was assessed by MTT assay. Also, the effects of the same drugs on the cancer cells migration were evaluated, using the wound healing assay. Lastly, the effects of que and dox were assessed on the expression of MMP-2 and MMP-9 genes. Results: The combination of 50 µMof que with 32 nM of dox was selected by CI comparison. The viability and migration of cancer cells and the gelatinases genes expression were decreased after treatment with individual drugs. The migration and the expression of MMP-2 and MMP-9 genes after treatment with the combination of que and dox was significantly reduced compared to the treatment with que and dox alone. Conclusions: Que inhibits the viability and migration of MDA-MB-231 cancer cells and synergistically enhances the effects of dox on the survival and migration of these cells. Hence, we propose this drug combination as a path for further research on breast cancer therapy. [ABSTRACT FROM AUTHOR]

Beauvericin (BEA) is a cyclic depsipeptide secondary metabolite of Fusarium species. It causes chemical hazards in food products and exists in an environment containing soil and various food types. On the other hand, the purified BEA has various biological activities and is regarded as a potential candidate for pharmaceutical research. This study was performed to assess the anti-proliferation activity of BEA against human breast cancer cells by regulating the estrogen receptor-alpha (ERα)/p38 pathway. TA and BA assays verified that BEA is a completed ER antagonist. Additionally, BEA suppressed cell proliferation in the anti-proliferation assay involving ER-positive human breast cancer cells co-treated with BPA and BEA. In respect to an anti-proliferation activity, the BPA-induced phosphorylation of p38 protein was inhibited in the presence of BEA. These results suggested that BEA exerts inhibitory potentials on endocrine disrupting effect and possibly acts as a natural therapeutic material for human estrogen hormonal health. [Display omitted] • BEA, a cyclic hexadepsipeptide was produced by Fusarium strain. • BEA has binding affinity to ERα, and suppressed homo-dimerization of ERαs in cytosol. • BEA determined to be an ERα antagonist in OECD PBTG No.455. • BEA suppressed the phosphorylation of p38 protein by exogenous estrogen. • This suppressing behavior caused the proliferation of ER-dependent breast cancer cells. [ABSTRACT FROM AUTHOR]

Sneha Mahalunkar,1 Amit Singh Yadav,2 Mahadeo Gorain,2 Vinay Pawar,3,4 Ranveig Braathen,5,6 Siegfried Weiss,3 Bjarne Bogen,5,6 Suresh W Gosavi,7 Gopal C Kundu2 1School of Basic Medical Science, Savitribai Phule Pune University, Pune 411007, Maharashtra, India; 2Laboratory of Tumor Biology, Angiogenesis and Nanomedicine Research, National Centre for Cell Science (NCCS), Pune 411007, India; 3Institute of Immunology, Hannover Medical School, Hannover, Germany; 4Department of Molecular Bacteriology, Helmholtz Centre for Infection Research, Braunschweig, Germany; 5K.G. Jebsen Centre for Influenza Vaccines Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; 6Oslo University Hospital, Oslo 0027, Norway; 7Department of Physics, Savitribai Phule Pune University, Pune 411007, Maharashtra, IndiaCorrespondence: Gopal C KunduLaboratory of Tumor Biology, Angiogenesis and Nanomedicine Research, National Centre for Cell Science (NCCS), Pune 411007, IndiaTel +91 202 570 8104Fax +91 202 569 2259Email kundu@nccs.res.in Suresh W GosaviDepartment of Physics, Savitribai Phule Pune University, Pune 411007, Maharashtra, IndiaTel +91 202 569 2678Fax +91 202 569 1684Email swg@physics.unipune.ac.inBackground: Curcumin has been widely used owing to its various medicinal properties including antitumor effects. However, its clinical application is limited by its instability, poor solubility and low bioavailability. Folic acid (FA)-functionalized nanoformulations may enhance the sustained release of an anticancer drug (curcumin) by tumor-specific targeting to improve therapeutic benefit. This study aims to design a nanoconjugate (NC) comprised of folate–curcumin-loaded gold–polyvinylpyrrolidone nanoparticles (FA–CurAu-PVP NPs) for targeted delivery in breast cancer model systems.Methods: We developed curcumin-loaded FA-functionalized Au-PVP NCs by layer-by-layer assembly. The folic acid–curcumin Au-PVP NCs (FA–CurAu-PVP NCs) were characterized by ultraviolet–visible spectra, Fourier transform infrared spectroscopy, X-ray powder diffraction and thermogravimetric analysis. In vitro anticancer and antimigratory effects of NCs were examined by performing MTT and wound migration assays. The in vivo antitumor efficacy of NCs was investigated using a preclinical breast cancer orthotopic mouse model.Results: Curcumin (40 μg/mL) was loaded along with conjugation of folate onto Au-PVP NPs to form FA–CurAu-PVP NCs. The size and charge of the NCs were increased gradually through layer-by-layer assembly and showed 80% release of curcumin at acidic pH. The NC did not show aggregation when incubated with human serum and mimicked an intrinsic peroxidase-like property in the presence of 3,3ʹ,5,5ʹ-tetramethylbenzidine substrate. The MTT data using these NCs showed efficient anticancer activity at lower doses in estrogen/progesterone receptor (ER/PR)-negative cells compared with ER/PR-positive cells. Furthermore, the NCs did not show cytotoxicity at the investigated concentration in human breast epithelial and mouse fibroblast cell lines. They showed inhibitory effects on cell migration and high antitumor efficacy in in vivo analysis.Conclusion: These results suggest that folate-based tumor targeting using CurAu-PVP NCs is a promising approach for tumor-specific therapy of breast cancer without harming normal cells.Keywords: curcumin, gold nanoconjugate, folic acid, breast cancer cell line, cytotoxic activity

The plant Caralliabrachiata (L) merr leaves and bark of the plant is still used by the rural people for medication. The aim of the work is to evaluate, presence of Phyto constituents, antibacterial, antifungal, anthelmintic, and anticancer activities of the leaves of the Carallibrachiata (L) merr. The presence of phyto constituents were screened using standard experimental protocol. The antibacterial activity was carried out by Agar disc diffusion method, the Antigungal activity was done by the well diffusion mtehod, the anthelmintic activity was carried against Indian earthworms Pheretimaposthuma, and the anti cancer activity was carried out by Sulforhodamine B method. The following phyto constituents such as Alkaloids, terpenoids, Saponins, Carbohydrates, Reducing Sugars, Flavanoids, Coumarines, Tannins, Steroids and proteins are present in the different extracts of C.brachiata (L) merr plant. The ethyl acetate extract exhibited remarkable zone of inhibition against gram positive and gram negative bacterial strains. The ethanol extract exhibited potent antifungal and anthelmintic activities, the anticancer activity of the ethyl acetate extract of the caralliabrachiata (Lour) merr, was performed using Sulforhodamine B method. The ethyl acetate and the ethanol extracts exhibited considerable zone of inhibition against the bacterial strains A. tumefaciens (12±0.4) as compared with the standard chloramphenicol (17±0.01). The ethanol extract exhibited moderate zone of inhibition against Aspergillus flavus and Curvularia sp (7±1.0and 17.3±0.88) as compared with the standard Flucanazole (10.6±1.15 and 25.3±1.45). Ethanol extract exhibited potent anthelmintic activity. [ABSTRACT FROM AUTHOR]

In this study we suggested a new strategy for drug delivery of 6-thioguanine (6-TG) as a cancer drug by loading of this thiolic drug at a surface of Au nanoparticles. For this goal, we synthesized Au nanoparticle (Au/NPs) by reduction of tetrachloroauric (III) acid solutions by sodium borohydride and characterized Au/NPs by X-ray powder diffraction (XRD), dynamic light scattering (DLS), Ultraviolet–visible spectroscopy (UV-Vis) and transmission electron microscopy (TEM) methods. Results showed good distribution of synthesized Au nanoparticle with diameter ~ 5 nm. In the second step, we loaded 6-thioguanine with strong Au-S bond by addition of this drug to Au nanoparticle suspension and characterized it by UV-Vis method. Furthermore, Au nanoparticle loaded with 6-thioguanine was utilized as a new system against breast cancer cell line (MCF7). IC50 for free 6-thioguanine, unloaded Au nanoparticle and 6-thioguanine loaded Au nanoparticle (6-TG/Au/NPs) were >15.0, 80.0 and 3.5 μg/ml, respectively. The results obtained revealed high cytotoxicity effect of 6-TG/Au/NPs on breast cancer cell line.

Micromelum minutum is used widely in traditional folk medicine. Although this species has been investigated extensively and several bioactive compounds have been isolated, little work has been done on Indonesian M. minutum. This research aimed to study the chemical constituents and biological activities of M. minutum cultivated in Bantimurung Bulusaraung National Park, South Sulawesi, Indonesia. The isolated compounds were assessed for their cytotoxicity towards MCF-7 and 4T1 cell lines by MTT method. The dried ground leaves of M. minutum were sequentially macerated with n-hexane, ethyl acetate, and methanol. The n-hexane and ethyl acetate extracts contained a flavonoid 5,7-dihydroxy-3,4',8-trimethoxyflavone (1) which inhibited MCF-7 and 4T1 cell viability by 50% at concentrations of 369±8 and 227±5 µM, respectively. Further separation of the ethyl acetate extract by column chromatography yielded acetyldihydromicromelin A (2) and a mixture of dihydromicromelin A (3) and dihydromicromelin B (4), which were not active toward MCF-7 and 4T1 cells. [ABSTRACT FROM AUTHOR]

In the search for alternative therapy for infections and other ailments, metallic nanoparticles, mainly silver nanoparticles (AgNPs) synthesized through bioengineered sources are extensively explored. Fungal bioactive compounds and their nanoparticles were reported with the potential biomedical application. A medicinal mushroom Ganoderma lucidum was reported as a repository of rich medicinal properties. In the current study, silver nanoparticles were synthesized using the extracts of G. lucidum and its antimicrobial activity was tested against drug-resistant Escherichia coli isolated from the catheter used for urinary tract infection (CAUTI). The GC–MS study of G. lucidum extracts showed the presence of ethyl acetoacetate ethylene acetal with the highest area percentage of 72.2% and retention time (RT 5873). Pyridine-3-ol is the second primary compound with a peak height of 6.44% and a retention time of 2.143. The third compound is l,4-Dioxane-2,3-diol, with an area of 8.09% and RT 5450. Butylated Hydroxy Toluene [BHT] is the fourth major compound with an area of 3.32%, and 9-Cedranone constitutes the fifth position in occupying the area percentage [1.88] and height 1.56%. Pyrrole is the sixth primary compound registering an area size of 0.96% and height 2.06%. The AgNPs synthesized using G. lucidum extract were in size range 23 and 58 nm as per SEM analysis and within the range wavelength 0.556–0.796 nm as per UV–Vis spectral study. FTIR Spectroscopy and X-ray diffraction analysis (XRD) were made to characterize the formed nanoparticles. The AgNPs synthesized effectively inhibited the growth of E. coli isolated from catheter-associated urinary tract infection and showed resistance to many drugs. The antioxidant potential of the synthesized nanoparticles assessed using DPPH radical scavenging activity, EC50 (µg/ml), and ARP data showed that the prepared nanoparticles were more potent in free radical scavenging activity than the standard quercetin. The cytotoxicity effect of Ag-NPs on breast cancer cell line- MDA-MB-231 confirmed its anticancer potential. The half-maximal inhibitory concentration (IC 50) of Ag-NPs to inhibit 50% of the tumor was 9.2 g/mL. The synthesized GL-AgNPs was exhibited a multifocal biomedical potential. [ABSTRACT FROM AUTHOR]

The mycelial extract of the entomopathogenic fungus Ophiocordyceps sobolifera has recently been reported to have anti-bacterial, anti-fungal and anti-cancer effects; however, there have been no reports on the medicinal value of the crude protein against the Michigan Cancer Foundation-7 (MCF-7) human breast cancer cell line. Therefore, in this study, crude proteins from 11 isolates of O. sobolifera were subjected to screening and evaluation for potential anticancer activity against a breast cancer cell line. The cytotoxic and antiproliferative effects of the crude proteins on human breast cancer MCF-7 cell line was investigated using the sulforhodamine B (SRB) assay and colony formation. The gene expression and cell cycle-associated protein levels were assayed by reverse transcription-quantitative polymerase chain reaction and western blotting analysis. The results showed that the crude proteins of all isolates had anti-cancer activity in a time- and dose-dependent manner. Among them, isolates Cod-KK1524, Cod-KK1630, Cod-KK1643 and Cod-KS1601 had greater inhibitory effects against cancer cells; therefore, these were chosen for further evaluation of anti-cancer mechanisms. These crude proteins exhibited a potent anticancer effect on the MCF-7 cells by inhibiting colony formation in a dose-dependent manner. Furthermore, the crude proteins significantly decreased the cyclin-dependent kinase 6 (cdk6) and cyclin D1 expression. Additionally, crude proteins significantly enhanced the potent cyclin-dependent kinase inhibitor (p21) levels, and reduced the expression level of the cell cycle protein, cyclin D1. These findings indicate that the crude protein of the entomopathogenic fungus O. sobolifera may be useful for developing an anti-cancer drug candidate for breast cancer therapeutic treatment. [ABSTRACT FROM AUTHOR]

Murraya koenigii (Linn.) Spreng, commonly known as curry leaf tree, is popular as a condiment and spice among Asian countries. Ethnobotanical studies suggest that certain phytochemicals in different parts of the plant are involved in anti-inflammatory, anti-oxidant and anti-cancer activities. There is a knowledge gap in connecting the ethnobotanical applications of M. koenigii, identification of chief phytochemicals through computational approaches and and evaluation of phytochemical's effect on cancer cell lines. We present here a comprehensive study to identify the phytochemicals responsible for anti-inflammation using random forest (RF) models, the interactions with COX-1 and COX-2 enzymes using molecular docking, dynamics simulation and free energy calculations. The RF models prioritised four phytochemicals viz. girinimbine, murrayanine, murrastinine-B and mukolidine with COX-1 and COX-2 binding potential. These phytochemicals developed key contacts with COX targets which were largely retained in the trajectories of the dynamics simulations. Phytochemicals ranking based on the binding free energy suggested that girinimbine (a carbazole alkaloid) is selective towards COX-2 supported by the experimental studies on COX anti-inflammation. Cytotoxicity assessment on the breast cancer cell line MDA-MB-231 illustrated that the presence of this phytochemical in root, stem and leaf (IC50 value: 0.006 µg/ml) parts highlight its role as a COX-2 inhibitor. [ABSTRACT FROM AUTHOR]

Breast cancer is the leading cause of cancer deaths among females in Malaysia. Ocimum tenuiflorum L., (O. tenuiflorum) commonly known as ruku in Malaysia, is usually cultivated as a garden ornamental plant because of its small purplish and some yellowish flower. The specific objective of this research is to investigate the anticancer of O. tenuiflorum against human breast cancer cell lines (MCF-7 and MDA-MB-231) and human fibroblast cell line (HS-27). In addition, another objective is to determine the mineral and heavy metal determination of O. tenuiflorum. O. tenuiflorum exhibited anticancer activity against MCF-7 (a hormone-dependent breast cancer cell line). The viability of MCF-7 cells decreased significantly after treatment with various concentrations of methanolic plant extracts (25 and 100 μg/mL), as shown via 3-(4,5-dimethylthiazol-2-yl)2,5-diphenyltetrazolium bromide (MTT) assay. The crude extracts show the lower IC50 (less than 100 μg/mL) value against the cancer cell lines and show no effect on HS-27. The high content of calcium in the leaves of O. tenuiflorum may play a role in decreasing the risk of certain cancer. The concentrations of heavy metals (Pb and As) detected in O. tenuiflorum are safe for consumption.

Background Heliotropium bacciferum , often known as wild heliotrope or wild quailplant, is a flowering plant from the borage family. This study examines the anti-metastatic impact of  H. bacciferum  on Michigan Cancer Foundation-7 (MCF-7) breast cancer cells and its ability to disrupt signaling pathways. Aim To explore the anti-metastatic effect of  H. bacciferum  on the MCF-7 breast cancer cell line. Materials and methods For this research, MCF-7 breast cancer cells were used. Cells were cultured and subjected to 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, as well as gene expression analysis for glycogen synthase kinase 3 beta (GSK3β), wingless-related integration site 2 (Wnt2), and β-catenin. The plant extract was tested to determine if it successfully blocked the signalling pathway or not.  Results The MTT test was performed to study the cytotoxic impact of  H. bacciferum.  At an increasing concentration of 100 μg/mL, the extract inhibited growth by 55%, whereas at 150 μg/mL, it inhibited growth by 52.5%. Maximum inhibition was seen at 150 μg/mL.  H. bacciferum  suppressed the GSK3β and Wnt2 signaling pathways in MCF-7 breast cancer cell lines, acting as an anti-metastatic and anticancer agent. The heliotrine compound in  H. bacciferum  showed high binding energy to metastatic targets such as GSK3β, Wnt2, and β-catenin. Moreover, chemical absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties also support the study. Conclusion In this study, we can infer that  H. bacciferum  has a favourable anticancer impact on MCF-7 breast cancer cell lines and may be utilised as an anticancer drug against breast cancer cells. It can also be further evaluated for different breast cancers and cell lines., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, R et al.)