Withaferin A-induced apoptosis in human breast cancer cells is mediated by reactive oxygen species.

摘要: Withaferin A (WA), a promising anticancer constituent of Ayurvedic medicinal plant Withania somnifera, inhibits growth MDA-MB-231 and MCF-7 human breast cancer cells in culture xenografts vivo association with apoptosis induction, but the mechanism cell death is not fully understood. We now demonstrate, for first time, that WA-induced mediated by reactive oxygen species (ROS) production due to inhibition mitochondrial respiration. WA treatment caused ROS cells, normal mammary epithelial line (HMEC). The HMEC was also resistant apoptosis. WA-mediated as well apoptotic histone-associated DNA fragment release into cytosol significantly attenuated ectopic expression Cu,Zn-superoxide dismutase both cells. resulting from exposure accompanied oxidative phosphorylation complex III activity. Mitochondrial DNA-deficient Rho-0 variants were production, collapse membrane potential, compared respective wild-type resulted activation Bax Bak SV40 immortalized embryonic fibroblasts derived double knockout mouse more mouse. In conclusion, present study provides novel insight molecular circuitry involving Bax/Bak.