Lifelong genistein feeding reduces colon neoplasia by affecting the expression profile of WNT signaling in AOM‐treated rats

Abstract

Colon cancer is a leading cancer worldwide. We investigated the effects of genistein (GEN) and soy protein isolate on the development of colon neoplasia in azoxymethane (AOM)-induced rats. Male Sprague-Dawley rats were exposed to a control (0 mg/kg of GEN), soy protein isolate (SPI, contains 140 mg/kg of GEN, aglycone equivalent), or genistein (140 mg/kg) diet throughout life, including gestation, lactation, and after weaning until the end of the study. Colon samples were collected at 6 w of age and analyzed for the baseline profile. The rest of rats were induced by AOM injection at 7 w of age and colon samples were collected at 13 w of age. Numbers of aberrant crypt foci (ACF) was determined in the descending colon. Offspring from all three dietary groups developed ACF. GEN and SPI diets decreased the numbers of total ACF/cm of colon, especially the numbers of higher multiplicity ACF/cm. Nuclear β-catenin level was not different between three diet groups at 6 w. However, SPI and GEN repressed AOM-induced Nuclear β-catenin accumulation at 13 w. Moreover, SPI and GEN maintained lower expression of WNT signaling including Wnt1, Wnt5a and WNT antagonists sFRP1, sFRP2 and sFRP5 compared to control after AOM treatment. Our results suggest that lifelong exposure to genistein reduces descending colon neoplasia by affecting WNT signaling and suppressing β-catenin accumulation in the AOM-induced rat model. Grant Funding Source: NIH