Genistein inhibits proliferation similarly in estrogen receptor-positive and negative human breast carcinoma cell lines characterized by P21WAF1/CIP1 induction, G2/M arrest, and apoptosis

Genistein has been proposed to be responsible for lowering the rate of breast cancer in Asian women but the mechanism for this chemopreventive effect in vivo is unknown. In this study, we present in vitro evidence that genistein inhibits cell proliferation similarly in ER-positive and ER-negative human breast carcinoma cell lines. This inhibition is associated with specific G(2)/M arrest and induction of p21(WAF1/CIP1) expression. Genistein results in a five- to six-fold increase in p21(WAF/CIP1) mRNA levels and a three- to four-fold increase in protein levels, only a 1.5-fold increase in p21(WAF1/CIP1) transcription but a three- to six-fold increase in p21(WAF1/CIP1) mRNA stability. The increase in p21(WAF1/CIP1) is followed by increased apoptosis. The similar effects of genistein on a number of breast carcinoma cell lines with different ER and p53 status suggest that the actions of genistein reported here are mediated through ER and p53 independent mechanisms. The chemopreventive effects of genistein in vivo could be mediated along an identical or similar anti-proliferative pathway. (C) 1998 Wiley-Liss, Inc.