Citrus nobiletin inhibits azoxymethane-induced large bowel carcinogenesis in rats

The inhibitory effects of dietary feeding of citrus nobiletin on azoxymethane (AOM)‐induced rat colon carcinogenesis using a long‐term bioassay were investigated. Five‐week old male F344 rats were initiated with two weekly subcutaneous injections of AOM (20 mg/kg bw) to induce colonic tumors. They were also given the diets containing 0.01% or 0.05% nobiletin for 34 weeks, starting one week after the last dosing of AOM. At the end of the study, the incidence of colonic adenocarcinoma were 67% in the AOM alone group, 55% in the AOM→0.01% nobiletin group, 35% (p < 0.05) in the AOM→0.05% nobiletin group. Also, nobiletin feeding reduced the cell‐proliferation activity, increased the apoptotic index, and decreased the prostaglandin E2 content in colonic adenocarcinoma and/or colonic mucosa. These findings might suggest that citrus nobiletin has chemopreventive ability against AOM‐induced rat colon carcinogenesis.