Preventive effects of isoflavones, genistein and daidzein, on estradiol-17beta-related endometrial carcinogenesis in mice

The effects of isoflavones (genistein and daidzein) on endometrial carcinog enesis in mice were investigated in two experiments. In the short-term expe riment (2 weeks), single subcutaneous (s.c.) administration of genistein [1 mg/30 g body weight (b.w.)] significantly decreased the levels of estradio l-17 beta (E-2) (5 ppm in diet)-induced expression of c-jun, interleukin-1 alpha (IL-1 alpha) and tumor necrosis factor-alpha (TNF-alpha) mRNAs in the uteri of ovariectomized mice (P<0.005, P<0.05 and P<0.01, respectively). D aidzein significantly inhibited E-2-induced expression of c-fos and IL-1<al pha> (P<0.01, P<0.01 respectively). In the long-term experiment (30 weeks), 140 female ICR mice were given N-methyl-N-nitrosourea-containing solution (1 mg/100 g b.w.) and normal saline (as controls) into their left and right uterine corpora, respectively. They were divided into six groups; group 1 was given E-2 (in diet) alone. Group 2 was given E-2 and genistein (1 mg/30 g b.w., s.c., every four weeks). Group 3 was exposed to E-2 and daidzein ( 1 mg/30 g b.w., s.c., every four weeks). Groups 4 and 5 respectively receiv ed genistein and daidzein, and were kept on the basal diet. Group 6 was kep t on the basal diet and served as a control. At the termination of the expe riment, incidences of endometrial, adenocarcinoma and atypical endometrial hyperplasia of the group given E-2 and genistein or daidzein were significa ntly lower than of the group with E-2 alone (P<0.01 and P<0.05, respectivel y). It is suggested that both genistein and daidzein have an inhibitory eff ect on estrogen-related endometrial carcinogenesis in mice, possibly by sup pressing expression of estrogen-induced estrogen-related genes c-fos and c- jun, and internal cytokines IL-1 alpha and TNF-alpha through a cytokine and estrogen receptor-mediated pathway.