Galectin-3 mediates genistein-induced G(2)/M arrest and inhibits apoptosis

Many recent studies have focused on potential chemopreventive activities of dietary genistein, a natural isoflavonoid compound found in soy products, Genistein has been implicated in anticancer activities, including different iation, apoptosis, inhibition of cell growth and inhibition of angiogenesis . In previous studies, genistein was shown to induce apoptosis and cell cyc le arrest at G(2)/M in several cancer cell lines ill vitro, which is associ ated with induction of p21(WAF1/CIP1),. universal inhibitor of cyclin-depen dent kinases. At present, the molecular basis for diverse genistein-mediate d cellular responses is largely unknown. In the present study, we investiga ted whether galectin-3, an anti-apoptotic gene product, regulates genistein -mediated cellular responses. We show that genistein effectively induces ap optosis without detectable cell cycle arrest in BT549, a human breast epith elial cell line which does not express galectin3 at a detectable level. In galectin-3 transfected BT549 cells, genistein induced cell cycle arrest at the G(2)/M phase without apoptosis induction. Interestingly, genistein indu ces p21(WAF1/CIP1) expression in galectin3-expressing BT549 cells, but not in control BT549 cells undergoing apoptosis, Collectively, the results of t he present study suggest that galectin3, at least in part, is a critical de terminant for genistein-mediated cell cycle arrest and apoptosis, and genis tein induction of p21(WAF1/CIP1) is associated with cell cycle arrest, but not required for apoptosis induction.