We have shown that dietary fish oil and pectin (FP) protects against radiation-enhanced colon cancer by upregulating apoptosis in colonic mucosa. To investigate the mechanism of action, we provided rats (n = 40) with diets containing the combination of FP or corn oil and cellulose (CC) prior to exposure to 1 Gy, 1 GeV/nucleon Fe-ion. All rats were injected with a colon-specific carcinogen, azoxymethane (AOM; 15 mg/kg), 10 and 17 days after irradiation. Levels of colonocyte apoptosis, prostaglandin E2 (PGE2), PGE3, microsomal prostaglandin E synthase-2 (mPGES-2), total β-catenin, nuclear β-catenin staining (%) and peroxisome proliferator-activated receptor δ (PPARδ) expression were quantified 31 weeks after the last AOM injection. FP induced a higher (P < 0.01) apoptotic index in both treatment groups, which was associated with suppression (P < 0.05) of antiapoptotic mediators in the cyclooxygenase (COX) pathway (mPGES-2 and PGE2) and the Wnt/β-catenin pathway [total β-catenin and nuclear β-catenin staining (%); P < 0.01] compared with the CC diet. Downregulation of COX and Wnt/β-catenin pathways was associated with a concurrent suppression (P < 0.05) of PPARδ levels in FP-fed rats. In addition, colonic mucosa from FP animals contained (P < 0.05) a proapoptotic, eicosapentaenoic acid-derived COX metabolite, PGE3. These results indicate that FP enhances colonocyte apoptosis in AOM-alone and irradiated AOM rats, in part through the suppression of PPARδ and PGE2 and elevation of PGE3. These data suggest that the dietary FP combination may be used as a possible countermeasure to colon carcinogenesis, as apoptosis is enhanced even when colonocytes are exposed to radiation and/or an alkylating agent.
All Science Journal Classification (ASJC) codes
- Cancer Research