The soy isoflavone genistein alters cell growth in non‐malignant colonocytes

Abstract

Numerous studies show that consumption of soy and its primary phytoestrogen genistein (Gen) can inhibit the formation of colon tumors. However, the effect of Gen at dietary levels in non-diseased colonocytes has not been investigated. The presented studies focused on evaluating the effects of Gen in non-malignant colonocytes in vitro and in vivo to determine how the compound influences the physiology of these cells. Gen treatments (1 and 10 μM/L) decreased cell growth, increased apoptosis, and increased p53 transcriptional activity in young adult mouse colonocytes (YAMC), a non-transformed cell line. However, these effects were lost when co-treated with an estrogen receptor beta (ERβ) antagonist. To further study the effects of Gen in healthy colonic epithelia, we evaluated physiologic changes in colonic crypts in ovariectomized mice given an Estradiol (E2) pellet, 1,000 ppm Gen diet, or a phytoestrogen free diet. As seen in vitro, E2 treated animals had significantly higher rates of apoptosis with Gen trending in the same fashion. These data demonstrate that Gen alters the physiology of non-malignant colonocytes which appears to be mediated through ERβ. Collectively, with our previous data, this suggests that Gen influences colonocyte physiology and this state may partially explain how this compound decreases risk of colon cancer. Grant support: American Institute for Cancer Research grant 07B080. Grant Funding Source: American Institute for Cancer Research grant 07B080