Inhibitory Effects of Phytoestrogens and Related Herbal Extracts on Mouse Endometrial Carcinogenesis: A Review

Abstract

The effects of isofiavones (genistein and daidzein) and related Kampo medicines (Juzen-taiho-to and Shimotsu-to) on endometrial carcinogenesis in mice were investigated separately in two experiments. In the short-term experiment (2 weeks), a single subcutaneous (s.c.) administration of genistein [(lmg/30g body weight (BW))] significantly decreased the levels of 17β-estradiol (E2; 5p.p.m. in diet)induced expression of c-jun, interleukin (IL)-1α and tumor necrosis factor (TNF)-α mRNAs in the uteri of ovariectomized mice (P < 0.005, P < 0.05, and P < 0.01, respectively). Daidzein significantly inhibited E2-induced expression of c-fos and IL-1α (P < 0.01 and P < 0.01, respectively). In the long-term experiment (30 weeks), the incidences of endometrial adenocarcinoma and atypical endometrial hyperplasia were significantly lower in the E2 group treated with either genistein or daidzein than in the corresponding control group (P < 0.01 and P < 0.05, respectively). In the shortterm experiment, Juzen-taiho-to or Shimotsu-to (Kampo formula) treatment (2 weeks) significantly decreased the levels of E2-stimulated expression of c-fos mRNA (P < 0.05). In the long-term experiment, Juzen-taiho-to and Shimotsu-to treatment significantly decreased the incidences of endometrial adenocarcinoma (P < 0.05) and other preneoplastic lesions under estrogenic stimulation. It is suggested that both genistein and daidzein, as well as Juzen-taiho-to, have an inhibitory effect on estrogen-related endometrial carcinogenesis in mice, indicated by the suppression of estrogen-related c-fos and c-jun, as well as the suppression of cytokine IL-1α and TNF-α-expression through a cytokine- and estrogen receptor-mediated pathway. Shimotsu-to is considered to be a key compounet of Juzen-taiho-to for the prevention of endometrial carcinoma.