Withaferin A-induced apoptosis in human breast cancer cells is associated with suppression of inhibitor of apoptosis family protein expression

The present study provides novel insight into the mechanism of apoptosis induction by withaferin A (WA), which is a bioactive constituent of an Ayurvedic medicine plant (Withania somnifera). Exposure of MDA-MB-231 and MCF-7 human breast cancer cells to WA resulted in suppression of XIAP, cIAP-2, and Survivin protein levels. The WA-induced apoptosis was significantly attenuated by ectopic expression of XIAP, Survivin, and cIAP-2 in both cells. However, the WA-mediated inhibition of MDA-MB-231 xenograft growth in vivo was associated with suppression of Survivin protein level only. These results indicate important contribution of Survivin suppression in WA-induced apoptosis.

► Withaferin A downregulates IAP family proteins in breast cancer cells. ► Overexpression of XIAP, cIAP-2 and Survivin confers protection against withaferin A-induced apoptosis. ► Withaferin A administration suppresses Survivin protein level in vivo.. ► Survivin may be a valid biomarker of withaferin A exposure and possibly response at least in breast cancer cells.