GENISTEIN IN THE CONTROL OF BREAST-CANCER CELL-GROWTH - INSIGHTS INTOTHE MECHANISM OF ACTION IN-VITRO

Genistein significantly inhibited cell growth (IC50 around 10 mu M) of MCF-7, MDAMB-231 and HBL-100 cell lines, but not of skin-derived fibr oblasts and counteracted the growth-stimulatory effects exerted by est radiol and growth factors. It abolished the paracrine stimulation obse rved in MCF-7 cells in co-culture with MDAMB-231 or fibroblasts. Genis tein-treated cells accumulated in the S and G(2)/M phases of the cell cycle and underwent apoptosis. Genistein decreased tyrosine phosphoryl ation induced upon treatment with transforming growth factor-alpha. Fi nally, genistein bound the estrogen receptor (ER) (relative affinity c onstant K-d = 4 nM), induced pS2 and cathepsin-D transcription and inc reased nuclear ER levels. (C) 1998 Elsevier Science Ireland Ltd. All r ights reserved.