Inducible cyclooxygenase (COX-2) and inducible nitric oxide synthase (iNOS/NOS-2) play pivotal roles as mediators of inflammation involved in early steps of carcinogenesis in certain organs. Therefore, chemoprevention is theoretically possible through inhibition of COX-2 and/or iNOS. In the present study, we examined the chemopreventive effects of indole-3-carbinol (I3C), a constituent of cruciferous vegetables (the family of Cruciferae) such as cabbages, cauliflowers and broccoli on the multiple intestinal neoplasia (Min) genetic mouse model, and on mouse colon carcinogenesis induced by azoxymethane (AOM). The consumption of cruciferous vegetables such as cabbage, broccoli, and Brussels sprouts has been shown to have cancer chemopreventive effects in humans and experimental animals. I3C has been shown to exert a cancer chemopreventive influence in liver, colon, and mammary tissue when given before or concurrent with exposure to a carcinogen. Powdered AIN-76A diets (Harlan Teklad Research Diet, Madison, USA) containing 100 or 300ppm I3C (group 1 or 2) or the same pellet diets without supplement (group 3) were fed to 6-week-old male C57BL/6J-ApcMin/+ (Min/+) mice (The Jackson Laboratory, Bar Harbor, ME, USA) for 10 weeks. In addition the same diets were given to wild-type normal C57BL/6J-ApcMin/+ littermates after AOM initiation (groups 4-7: 10 mice in each group) for 32 weeks from week 4. At 16 weeks of age, all Min/+ mice (groups 1-3) were sacrificed for assessment of intestinal polyp development. The incidences of the colonic adenomatous polyps in the groups 1-3 were 60% (12/20), 60% (15/25) and 84% (21/25), respectively. A decreasing tendency in multiplicities of the colonic adenomatous polyps in group 1 (I3C 100ppm; 0.85±0.22; 61%) and group 2 (I3C 300ppm; 1.32±0.28; 94%) was observed when compared with group 3 (control; 1.40±0.21; 100%). Total number of aberrant crypt foci (ACF)/colon or aberrant crypts (AC)/colon in wild-type mice of group 4 or 5 were decreased significantly compared with those of the AOM alone group (group 6) (P<0.01). These results suggest that I3C may be a potential chemopreventive agent for colon cancer.
|Number of pages||9|
|Journal||Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis|
|Publication status||Published - 2003 Jan 1|
All Science Journal Classification (ASJC) codes
- Molecular Biology
- Health, Toxicology and Mutagenesis