Abstract PR-13: Inhibition of chronic colitis-induced carcinogenesis in IL-10 knockout mice by dietary supplementation of black raspberries

PR-13

Epidemiological and experimental studies indicate that inflammation is associated with the development of colon cancer. For example, it is known that patients with ulcerative colitis have an increased incidence of colon cancer, and anti-inflammatory drugs and bioactive food components that suppress colonic inflammation reduce the risk of colon cancer. IL-10 is an important regulatory anti-inflammatory cytokine associated with the development of colonic colitis. 100% of IL-10 knockout (KO) mice develop colitis after 3 months of age; histopathology reveals transmural inflammation, predominantly in the cecum. We have shown that the administration of a diet containing twice the recommended amount of iron leads to the development of colonic adenocarcinoma in more than 80% of IL-10 KO mice within 5 months. In the present study, we evaluated the effects of a dietary supplementation of black raspberries on spontaneous colitis-induced carcinogenesis in IL-10 KO mice. Beginning at 4 weeks of age, mice were administered black raspberry powder in AIN-93G diet at concentrations of 5% and 10% until termination of the experiment at 23 weeks. The colorectal tumor incidence in IL-10 KO mice fed control AIN-93G diet was 71.4% (10/14 mice with tumors). Significant reductions in colonic tumor incidence [38% (5/13 mice) and 30.8% (4/13 mice)] were observed in mice receiving 5% and 10% black raspberry diets, respectively. Histopathologic analysis of chronic inflammatory activity in the colon showed that the berries significantly inhibited the overall inflammatory index, including the extent of inflammation, ulcer formation and epithelial hyperplasia. Mechanistic studies suggest that inhibition of colitis-associated carcinogenesis by dietary berries might relate to their effects on modulation of myeloperoxidase-labeled inflammatory cells, nitro-oxidative stress, and cell proliferation. We conclude that black raspberries, as a food-based prevention agent, have potential for the prevention of inflammation-related carcinogenesis in the colon. (Supported by NIH grants R01-CA104741 and -CA103180).

Citation Information: Cancer Prev Res 2008;1(7 Suppl):PR-13.