Abstract 957: Dietary flavonols protect against colorectal carcinogenesis in an AOM-DSS mouse model for colorectal cancer

Abstract

Abstract Background: Epidemiological studies suggest that a flavonol-rich diet inhibits colorectal carcinogenesis. Flavonols are a subgroup of polyphenols, which are found in fruits and vegetables usually glycosylated and are in particularly high concentrations in dry beans, onions, apples, and tea. The most consumed individual flavonols are in this order quercetin and one of its glycosylated forms rutin, kaempferol, myricetin, and isorhamnetin. Aim: To determine which individual flavonol is most protective against colorectal carcinogenesis in an inflammation-associated mouse colorectal carcinogenesis model (azoxymethane[AOM]/dextran sodium sulfate[DSS]-induced FVB mice). Methods: At 6 weeks of age, mice were injected intraperitoneally with AOM (10 mg/kg body weight). Mice then received for 1 week 2% DSS in the drinking water (1 or 1 and 4 weeks after AOM injection). Three days after the last DSS cycle, mice either remained on the AIN-93G diet or were switched to one enriched with 500 mg of kaempferol or equimolar concentrations of isorhamnetin, myricetin, quercetin, or rutin/kg of diet. Mice (n=32/group) remained for 85 days on the diets unless they had to be sacrificed earlier because of morbidity. A subset of mice was imaged using magnetic resonance imaging (MRI) at various times throughout the study. Results: Among the diets, mice on the control diet had the highest morbidity (50%) and mice on the isorhamnetin diet had the lowest morbidity (22%). Similarly, lesion number and size were lowest in mice on the isorhamnetin (16/mouse and 8.8 mm3/lesion) and the kaempferol (15/mouse and 7.4 mm3/lesion) diet compared to the control diet (21/mouse and 11.6 mm3/lesion). Image parameters detected different stages of colorectal carcinogenesis that can be modified by diet. Conclusion: All individual flavonols showed some protection against colorectal carcinogenesis with isorhamnetin and kaempferol being most efficacious. Studies are underway to identify serum, tissue, and imaging biomarkers of efficacy at earlier stages of colorectal carcinogenesis. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 957.