Biochanin A promotes proliferation that involves a feedback loop of microRNA-375 and estrogen receptor alpha in breast cancer cells.

ABSTRACT

BACKGROUND: Biochanin A and formononetin are O-methylated isoflavones that are isolated from the root of Astragalus membranaceus, and have antitumorigenic effects. Our previous studies found that formononetin triggered growth-inhibitory and apoptotic activities in MCF-7 breast cancer cells. We performed in vivo and in vitro studies to further investigate the potential effect of biochanin A in promoting cell proliferation in estrogen receptor (ER)-positive cells, and to elucidate underlying mechanisms. METHODS: ERα-positive breast cancer cells (T47D, MCF-7) were treated with biochanin A. The MTT assay and flow cytometry were used to assess cell proliferation and apoptosis. mRNA levels of ERα, Bcl-2, and miR-375 were quantified using real-time polymerase chain reaction. Compared with the control, low biochanin A concentrations (2-6 µM) stimulated ERα-positive cell proliferation (T47D, MCF-7). The more sensitive T47D cells were used to study the relevant signaling pathway. RESULTS: After treatment with biochanin A, ERα, miR-375, and Bcl-2 expression was significantly upregulated. Additionally, in the in vivo studies, uterine weight in ovariectomized mice treated with biochanin A increased significantly. CONCLUSION: This study demonstrated that biochanin A promoted ERα-positive cell proliferation through miR-375 activation and this mechanism is possibly involving in a miR-375 and ERα feedback loop.