TPGS loaded triphenyltin (IV) micelles induced apoptosis by upregulating p53 in breast cancer cells and inhibit tumor progression in T-cell lymphoma bearing mice.

AIMS

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.

METHODS

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.

KEY FINDINGS

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.

SIGNIFICANCE

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.