Effects of quercetin and β-carotene supplementation on
azoxymethane-induced colon carcinogenesis and inflammatory responses in rats
fed with high-fat diet rich in ω-6 fatty acids
Issue title: Free Radicals in Biology and Medicine: From
Inflammation to Biotechnology
Affiliations: Department of Food and Nutrition, Sookmyung Women's
University, Seoul, Korea | Department of Food Science and Nutrition, Hallym
University, Chuncheon, Korea | Department of Animal Science and Biotechnology,
Kyungpook National University, Daegu, Korea | Cancer Prevention & Early Detection Branch,
Division of Cancer Control and Epidemiology, National Cancer Center, Goyang,
Korea | Faculty of Health and Social Care, London South Bank
University, London SE1 0AA, UK
Note: [] Address for correspondence: Mi-Kyung Sung, Ph.D., Department of
Food and Nutrition, Sookmyung Women's University, 52 Hyochangwon-gil,
Yongsan-gu, Seoul, 140-742 Korea. Tel.: +82 2 710 9395; E-mail:
[email protected]
Abstract: Chronic inflammation in gastrointestinal tract has been suggested as
a risk factor for tumor formation. The effect of dietary supplementation of
quercetin or ß-carotene on colon carcinogenesis and inflammatory response
in rats fed with high-fat diet rich in ω-6 fatty acids was assessed.
Animals were exposed to two weekly subcutaneous injections of AOM
(azoxymethane) at a single dose of 15 mg/kg body weight. A portion of rats from
each group was sacrificed at 8 weeks after the last AOM treatment to determine
ACF (aberrant crypt foci) formation. Colonic mucosa expression of iNOS
(inducible nitric oxide) and COX-2 (cyclooxygenase-2) protein, and blood
PGE_{2} (prostaglandin E_{2}) level were
measured. The remaining groups of animals were sacrificed at 33 weeks after the
last AOM treatment to examine colon tumor formation. Rats on high-fat diet
developed more aberrant crypt foci (P<0.05) compared with those of rats on
regular diet. In the same vein, but in contrast to the effect seen with regular
diet, the high-fat diet induced a significant up-regulation of iNOS expression.
There was no significant change in the extent of COX-2 expression or in the
PGE_{2} levels. Quercetin or β-carotene supplementation
reduced the number of ACF only in animals fed high-fat diet (p<0.05),
however, no significant difference in tumor incidence was found. At week 33,
the expression of iNOS was reduced by quercetin without a statistical
significance, and COX-2 expression was slightly reduced in rats on
ß-carotene supplementation. No change in PGE_{2}
levels was observed. Whilst dietary antioxidants are considered as effective
suppressors for precancerous lesion formation in colons exposed to high-risk
diet, it is clear that elucidating the role of individual antioxidants in colon
tumor formation coupled with an understanding of the molecular mechanisms
involved would benefit colon cancer prevention strategies.
