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

Menée à l'aide d'un modèle murin, cette étude évalue l'effet chimiopréventif d'une supplémentation en glutamine sur la tumorigenèse du côlon associée à une colite induite par des agents chimiques

Résumé en anglais

Chronic colonic inflammation is a known risk factor for colorectal cancer (CRC). Glutamine (GLN) supplementation has shown its anti-inflammation benefit in experimental colitis. Whether GLN is effective in preventing colon carcinogenesis remains to be investigated. The chemopreventive activity of GLN was evaluated in the mouse model of dextran sulfate sodium (DSS)/azoxymethane (AOM)-induced colitis-associated CRC in our study. Mice were treated with DSS/AOM and randomized to receive either a control diet or GLN-enriched diet intermittently of the study. The disease activity index was evaluated weekly. On day 80 of the experiment, the entire colon and rectum were processed for histopathologic examination and further evaluation. Proinflammatory mediators and cytokines were measured by ELISA, RT-PCR and Western blot analysis. Here we show that after GLN-enriched diet, the colitis presented a statistical improvement, tumors burden decreased significantly. This was accompanied by lower activity of NF-κB, decreased expression of COX-2 and iNOS, lower expression of cytokines and chemokines as well as reduced proliferation and induced apoptosis in the colons of colitis-associated CRC mice. Our data demonstrate the protective/preventive effect of GLN in the progression of colitis-associated CRC, which was correlated with a dampening of inflammation and NF-κB activity and with a decrease of inflammatory protein over-expression.