ESTROGENIC EFFECTS OF GENISTEIN ON THE GROWTH OF ESTROGEN RECEPTOR-POSITIVE HUMAN BREAST-CANCER (MCF-7) CELLS IN-VITRO AND IN-VIVO

Genistein, found in soy products, is a phytochemical with several biol ogical activities. In the current study, our research focused on the e strogenic and proliferation-inducing activity of genistein, We have de monstrated that genistein enhanced the proliferation of estrogen-depen dent human breast cancer (MCF-7) cells in vitro at concentrations as l ow as 10 nag with a concentration of 100 nM achieving proliferative ef fects similar to those of 1 nM estradiol. Expression of the estrogen-r esponsive gene pS2 was also induced in MCF-7 cells in response to trea tment with a concentration of genistein as low as 1 mu M. At higher co ncentrations (above 20 mu M), genistein inhibits MCF-7 cell growth. In vivo, we have shown that dietary treatment with genistein (750 ppm) f or 5 days enhanced mammary gland growth in 28-day-old ovariectomized a thymic mice, indicating that genistein acts as an estrogen in normal m ammary tissue, To evaluate whether the estrogenic effects observed in vitro with MCF-7 cells could be reproduced in vivo, MCF-7 cells were i mplanted s.c. in ovariectomized athymic mice, and the growth of the es trogen-dependent tumors was measured weekly, Negative control animals received the American Institute of Nutrition (AIN)-93G diet, the posit ive control group received a new s.c. estradiol (2 mg) pellet plus the AIN-93G diet, and the third group received genistein at 750 ppm in th e AIN-93G diet. Tumors were larger in the genistein (750 ppm)-treated group than they were in the negative control group, demonstrating that dietary genistein was able to enhance the growth of MCF-7 cell tumors in vivo. Increased uterine weights were also observed in the genistei n-treated groups. In summary, genistein can act as an estrogen agonist in vivo and in vitro, resulting in the proliferation of cultured huma n breast cancer cells (MCF-7) and the induction of pS2 gene expression , Here we present new information that dietary genistein stimulates ma mmary gland growth and enhances the growth of MCF-7 cell tumors in ova riectomized athymic mice.