ESTROGENIC AND ANTIPROLIFERATIVE PROPERTIES OF GENISTEIN AND OTHER FLAVONOIDS IN HUMAN BREAST-CANCER CELLS IN-VITRO

Experimental and epidemiologic studies support the view that soyfoods prevent cancer as well as diseases and symptoms associated with estrog en deficiency. Recent research suggests that the isoflavonoid genistei n, a phytoestrogen found in abundance in soyfoods, may be one of the p rincipal molecular components responsible for these health benefits. I n this study we investigated the effects of a broad physiologically re levant concentration range of genistein on estrogen receptor (ER) bind ing, induction of the estrogen-regulated antigen pS2, and cell prolife ration rate in ER(+) and ER(-) human breast cancer cells grown in vitr o. Dose response to genistein was compared with that of estradiol, tam oxifen, and several other structurally similar iso- and bioflavonoids (e.g., equol, kaempferol, and quercetin). Our results revealed that ge nistein has potent estrogen agonist and cell growth-inhibitory actions over a physiologically achievable concentration range (10 nM-20 mu M) . Other flavonoids over the same concentration range were good estroge n agonists and poor cell growth inhibitors (equol) or poor estrogen ag onists and potent growth inhibitors (kaempferol and quercetin). The gr owth-inhibitory actions of flavonoids were distinctly different from t hose of triphenyl antiestrogens like tamoxifen. In summary, our result s reveal that genistein is unique among the flavonoids tested, in that if has potent estrogen agonist and cell growth-inhibitory actions ove r a physiologically relevant concentration range.