Daidzein causes cell cycle arrest at the G1 and G2/M phases in human breast cancer MCF-7 and MDA-MB-453 cells

We examined the mechanisms by which daidzein inhibits the growth of breast cancer cells. First, we investigated its antiproliferative effects in MCF-7 and MDA-MB-453 cells exposed to 1-100 mu M daidzein for 24, 48, or 72 h. Daidzein significantly inhibited cell proliferation in a dose- and time-dependent manner (p < 0.05) and resulted in significant cell cycle arrest in the G1 and G2/M phases after 72h of treatment at concentrations over 5 and 10 mu M in MCF-7 and MDA-MB-453 cells, respectively (p < 0.05). In addition, daidzein caused the accumulation of cells in sub-GO phase in a dose-dependent manner in MDA-MB-453 (p < 0.05), but not MCF-7, cells. As another biomarker of apoptosis induction, caspase-9 activity was significantly increased by daidzein in both cells. To investigate the effects of daidzein on the proteins regulating cell cycle arrest, cells were treated with 100 mu M daidzein for 72 h. Similar changes in the expression of regulatory proteins were detected in both cells. Daidzein treatment resulted in decreases in cyclin D, CDK2, and CDK4, whereas the expression of CDK6 and cyclin E was unchanged. The protein expression of CDK1 related to the G2/M phase decreased markedly with daidzein treatment, whereas slight expression of cyclins A and B occurred. Daidzein treatment increased the expression of the CDK inhibitors p21(Cip1) and p57(Kip2), but not that of P27(Kip1). Thus, daidzein exerts its anticancer effects in human breast cancer cells via cell cycle arrest at the G1 and G2/M phases. (C) 2008 Elsevier GmbH. All rights reserved.