Genistein, a soya isoflavone, prevents azoxymethane-induced up-regulation of WNT/ beta-catenin signalling and reduces colon pre-neoplasia in rats.

摘要

The present study aimed to explore the role(s) of the soya isoflavone genistein (GEN) in preventing the development of colon pre-neoplasia, using Wingless/int (WNT)/ beta-catenin as a molecular marker of colon abnormality. Specifically, the effects on the WNT/ beta-catenin signalling pathway from GEN were examined by using an azoxymethane (AOM)-induced rat colon cancer model. Male Sprague-Dawley rats were fed a control (CTL), a soya protein isolate (SPI) or a GEN diet from gestation to 13 weeks of age. The first sampling was conducted at 7 weeks of age for pre-AOM analysis. The remaining rats were injected with AOM at 7 weeks of age. The descending colon was collected 6 weeks later for the evaluation of aberrant crypt foci (ACF), gene expression and nuclear protein accumulation. AOM injection induced aberrant nuclear accumulation of beta-catenin in the CTL group but not in the SPI or GEN group. Moreover, the WNT target genes Cyclin D1 and c-Myc were repressed by SPI and GEN. Meanwhile, SPI and GEN suppressed the expression of WNT signalling genes including Wnt5a, Sfrp1, Sfrp2 and Sfrp5 to the similar level to that of the pre-AOM period. Rats fed SPI and GEN had a decreased number of total aberrant crypts. GEN feeding also resulted in a reduced number of ACF with N = 3 per foci. The reduction of WNT/ beta-catenin signalling was correlated with the decrease in total aberrant crypts. By testing WNT/ beta-catenin signalling as a biomarker of colon carcinogenic potential, we showed the novel role of GEN as a suppressor of carcinogen-induced WNT/ beta-catenin signalling in preventing the development of early colon neoplasia.