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Singh, Mamata; Singh, Virendra; Basu Baul, Tushar S.; Koch, Biplob
Life sciences (1973), 11/2022, Volume: 308Journal Article
Currently, breast cancer is one of the most frequently diagnosed and the second leading cause of cancer related deaths in women worldwide. Our present study aimed to investigate the major mechanistic effects of micelles (TSD-30-F, TSD-34-F) on breast cancer cells as well as their antitumor efficacy in in vivo DL bearing BALB/c mice. Apoptotic death by micelles was investigated by mitochondrial aggregation, membrane potential and DNA fragmentation assay in MCF-7 and MDA-MB-231 cells. Molecular mode of action of micelles were determined by RT-PCR and western blot analysis, drug-ligand interaction was analyzed by in silico methods, while, in vivo antitumor activity was investigated by Kaplen-Meier survival curve, T/C value, body weight and belly size of BALB/c mice. TSD-30-F and TSD-34-F micelles displayed significant apoptotic induction. At molecular level, TSD-30 and TSD-34 micelles showed up-regulation of p53, Bax, Bak, Caspase-3 and down-regulation of Bcl-2 genes as well as proteins in tested breast cancer cells. In silico analysis revealed that TSD-30 and TSD-34 showed efficient binding affinity with p53, Caspase-3, Bax and Bcl-2 proteins. Significant in vivo antitumor efficacy was exhibited by the micelles formulations by increasing life span with reduced bodyweight and belly size growth pattern in BALB/c mice compared to DTX-F micelles. Our results suggest that triphenyltin (IV) micelles could be a very promising therapeutic candidate for treatment of breast cancer patients and occupy a new place in targeted breast cancer therapeutic. Display omitted •Triphenyltin (IV) micelles induced mitochondrial mediated apoptosis in breast cancer.•Micelles induced apoptosis by p53 upregulation, and down regulation of Bcl-2.•Micelles enhanced antitumor efficacy in DL bearing BALB/c mice than DTX-F micelles.
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