Fish oil and pectin enhance apoptosis in irradiated rat colonocytes via suppression of PGE synthase‐2 and Wnt pathway

Abstract

We have previously shown a synergistic protective effect of the combination of fish oil and pectin on both colon tumor incidence and enhancement of spontaneous apoptosis. We hypothesized that a diet containing fish oil and pectin may enhance apoptosis through suppression of the prostaglandin and Wnt pathways (fish oil) and activation of death receptor-mediated apoptosis (pectin). To test this hypothesis, rats were provided diets containing either fish oil/pectin or corn oil/cellulose. We injected all rats with azoxymethane (15 mg/kg body wt), a colon specific carcinogen, during the 3rd and 4th week after starting the diets. Rats were exposed to 1 Gy, 1 GeV/nucleon Fe-ion radiation. Apoptosis (TUNEL assay), and PGE synthase-2, PPARβ /δ, and β-catenin (Western blots) were determined 31 wk after the last AOM injection. A fish oil/pectin diet suppressed (P = 0.03) PGE synthase-2 levels compared to the corn oil/cellulose diet. PPARβ/ δ (P = 0.06) and β-catenin (P = 0.06) levels also showed a similar trend. Apoptosis was enhanced (P = 0.03) in irradiated rats consuming a fish oil/pectin diet. These data suggest that enhanced apoptosis observed in irradiated rats consuming a fish oil/pectin diet could be attributed to lower PGE synthase-2, PPARβ/ δ and β-catenin levels. Thus, this study provides evidence that the mechanism of action by which the fish oil and pectin diet induces apoptosis in radiation exposed rats at the tumor stage involves the PGE2 and Wnt pathways. Funded by AICR 05B094, NIH CA61750, CA82907, NSBRI NASA NCC 9-58, and NIEHS P30-ES09106.