Chemopreventive effect of dietary glutamine on colitis-associated colon tumorigenesis in mice

Abstract

Chronic colonic inflammation is a known risk factor for colorectalcancer (CRC). Glutamine (GLN) supplementation has shownits anti-inflammation benefit in experimental colitis. WhetherGLN is effective in preventing colon carcinogenesis remains tobe investigated. The chemopreventive activity of GLN was evaluatedin the mouse model of dextran sulfate sodium (DSS)/azoxymethane(AOM)-induced colitis-associated CRC in this study. Mice were treated with DSS/AOM and randomized to receiveeither a control diet or GLN-enriched diet intermittently of thestudy. The disease activity index was evaluated weekly. On day80 of the experiment, the entire colon and rectum were processedfor histopathologic examination and further evaluation. Pro-inflammatory mediators and cytokines were measured byenzyme-linked immunosorbent assay, real-time-PCR and westernblot analysis. Here, we show that after GLN-enriched diet, the colitis presented a statistical improvement and tumors burdendecreased significantly. This was accompanied by lower activityof nuclear factor-κB (NF-κB), decreased expression of cyclooxygenase-2 and inducible nitric oxide synthase, lower expression ofcytokines and chemokines as well as reduced proliferation andinduced apoptosis in the colons of colitis-associated CRC mice. Our data demonstrate the protective/preventive effect of GLN inthe progression of colitis-associated CRC, which was correlatedwith a dampening of inflammation and NF-κB activity and with adecrease of inflammatory protein overexpression. © The Author 2013. Published by Oxford University Press. All rights reserved.