Effects of oligosaccharide, soy isoflavone and their interactions on colonic aberrant crypt foci and cyclooxygenase‐2 expression in dimethylhydrazine‐treated rats

Abstract

Effects of soy isoflavone and fructooligosaccharide on colonic aberrant crypt foci (ACF), the surrogate end-point biomarker for colorectal cancer, and cyclooxygenase-2 (COX-2) expression were investigated in dimethylhydrazine (DMH)-treated rats. Sprague Dawley male rats were injected DMH to induce colorectal cancer, and given one of experimental diets containing 0, 3, 6, 9% of fructooligosaccharide with or without soy isoflavone (100 mg/100 g diet) for 12 weeks. Fixed distal colon was stained in 0.2% methylene blue for 10–15 min and then scored for aberrant crypts (AC) on the mucosal side of the colon at 40 x magnification. The number of colonic ACF and the number of AC observed in each focus were recorded. Western blot analysis of COX-2 protein in the colonic epithelial tissues was carried out. Using two-way ANOVA, interactive effects of soy isoflavone and dose of fructooligosaccharide on ACF formation and COX-2 expression were tested. DMH-treated control rats showed significantly increased ACF numbers and COX-2 expression compared with normal rats. The number of ACF, the number of ACF equal to or more than 4 AC per ACF, and COX-2 expression were significantly decreased dose-dependently in fructooligosaccharide-fed groups (P < 0.001) treated with DMH. Soy isoflavone significantly decreased the number of ACF equal to or more than 4 AC per ACF (P < 0.001) and COX-2 expression (P < 0.01). There were statistically significant interactions between dose of fructooligosaccharide and soy isoflavone on ACF formation and on COX-2 expression. In conclusion, combination of oligosaccharide and soy isoflavone facilitated inhibition of colonic aberrant crypt foci and cyclooxygenase-2 expression in DMH-treated rats.