Preventive Effects of Isoflavones, Genistein and Daidzein, on Estradiol-17beta-related Endometrial Carcinogenesis in Mice

The effects of isoflavones (genistein and daidzein) on endometrial carcinogenesis in mice were investigated in two experiments. In the short-term experiment (2 weeks), single subcutaneous (s.c.) administration of genistein [1 mg / 30 g body weight (b.w.)] significantly decreased the levels of estradiol-17beta (E(2)) (5 ppm in diet)-induced expression of c-jun, interleukin-1alpha (IL-1alpha) 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). Daidzein significantly inhibited E(2)-induced expression of c-fos and IL-1alpha (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 received genistein and daidzein, and were kept on the basal diet. Group 6 was kept on the basal diet and served as a control. At the termination of the experiment, incidences of endometrial adenocarcinoma and atypical endometrial hyperplasia of the group given E(2) and genistein or daidzein were significantly lower than of the group with E(2) alone (P < 0.01 and P < 0.05, respectively). It is suggested that both genistein and daidzein have an inhibitory effect on estrogen-related endometrial carcinogenesis in mice, possibly by suppressing expression of estrogen-induced estrogen-related genes c-fos and c-jun, and internal cytokines IL-1alpha and TNF-alpha through a cytokine and estrogen receptor-mediated pathway.