Isoflavone and its metabolite equol inhibit development of azoxymethane-induced colorectal tumors and modulate proliferation of colon carcinoma cells

Although previous studies have demonstrated the inhibiting ability of isoflavones on the development of colorectal cancer, the effects and mechanisms of its metabolite equol on colorectal cancer remain unclear. To determine the effects of equol on the development of colorectal tumors, in vivo and in vitro, the present study induced colorectal tumors in bilaterally ovariectomized female Sprague-Dawley rats as postmenopausal rat models using azoxymethane, culturing the human colon carcinoma cell lines SW480 and HCT-15. RT-PCR and Western blotting were performed to examine mRNA and protein expression of two estrogen receptors (ER alpha and ER beta) and nuclear factor (erythroid-derived 2)-like 2 (Nrf2). Moreover, concentrations of thiobarbituric acid reactive substance, 8-hydroxyguanosine, and superoxide dismutase in rat blood serum were examined. Equol treatment reduced the incidence of colon tumors and inhibited the proliferation of both colon carcinoma cells, in a dose-dependent manner. RT-PCR and Western blotting results showed that equol treatment significantly upregulated expression of Nrf2 and ER beta, in vivo and in vitro. Moreover, genistein and equol treatment groups significantly reduced concentrations of thiobarbituric acid reactive substances and increased concentrations of superoxide dismutase. Present results suggest that equol may significantly inhibit the development of colorectal tumors by Nrf2-induced antioxidant activity and upregulating expression of ER beta.