d-a-Tocopheryl Polyethylene Glycol 1000 Succinate and a small-molecule Survivin suppressant synergistically induce apoptosis in SKBR3 breast cancer cells

Abstract

Breast cancer is the second in mortality rate malignancy among women. Despite the many advances in breast cancer treatment, there is still a need to improve drug efficacy and reduce non-specific effects. D-alpha-tocopheryl polyethylene glycol succinate (TPGS) is frequently used in the development of drug delivery systems to improve the pharmacokinetics of anti-cancer drugs and reduce multi-drug resistance. We have previously shown that TPGS not only acts as a carrier molecule but also exerts anti-cancer effects. As part of this study, we investigated the effect of TPGS with YM155, a small molecule suppressant of Survivin, in various breast cancer cell lines representing different subtypes of the disease. We aimed to evaluate the presumed synergistic effect of the TPGS-YM155 combination and reveal its mechanism of action. Our results show that the TPGS-YM155 combination acts synergistically to reduce specifically the viability of SKBR3 cells. The combination of these agents reduced activation of the AKT pathway, decreased Survivin and Bcl-2 levels, and induced caspase-dependent and independent apoptosis via the mitochondrial pathway. Importantly, the TPGS-YM155 combination did not significantly affect the viability of MCF-10A normal immortalized cells. In conclusion, the combination of YM155 and TPGS could be a promising approach against SKBR3-type breast cancer.