Genistin attenuates cellular growth and promotes apoptotic cell death breast cancer cells through modulation of ERalpha signaling pathway

Abstract

Estrogen receptor alpha (ERα) is a vital molecular target in ER-positive breast cancer. Genistin (GS) is one of isoflavones that can exert diverse pharmacological effects including that of anti-proliferation, anti-tumor angiogenesis, induce cell cycle arrest and apoptosis. Here, we examined the efficacy of GS as an anti-cancer agent against breast cancer cells. We observed that GS exhibited more cytotoxic activity against MCF-7 cells than MDA-MB-231cells. We found that GS caused negative regulation of ERα. It also effectively down-modulated ER nuclear translocation as well DNA binding activity in breast cancer cells. Moreover, GS effectively induced apoptosis and suppressed levels of oncogenic markers in MCF-7 cells. Interestingly, in ERα knocked-down MCF-7 cells, cell viability was found to be increased and the levels of cleaved PARP was abolished. We found completely contrasting results in ERα overexpressed MDA-MB-231 cells, where cell viability was decreased and expression level of apoptotic markers was enhanced. Our results demonstrate that GS can suppress ERα signaling and can be useful for prevention and therapy of ER-positive breast cancer.