title: Chemopreventive effect of dietary glutamine on colitis-associated colon tumorigenesis in mice.
abstract: 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 this 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. Pro-inflammatory mediators and cytokines were measured by enzyme-linked immunosorbent assay, real-time-PCR and western blot analysis. Here, we show that after GLN-enriched diet, the colitis presented a statistical improvement and tumors burden decreased significantly. This was accompanied by lower activity of nuclear factor-κB (NF-κB), decreased expression of cyclooxygenase-2 and inducible nitric oxide synthase, 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 overexpression.
authors.affiliation: Department of Oncology, the Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Tian
authors.forename: Keming
authors.initials: K
authors.lastname: Wang
authors.forename: Zhaoxia
authors.initials: Z
authors.lastname: Wang
authors.forename: Nan
authors.initials: N
authors.lastname: Li
authors.forename: Guozhong
authors.initials: G
authors.lastname: Ji
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology; D017209:Apoptosis; D001397:Azoxymethane / Q000009:adverse effects; D014408:Biomarkers, Tumor / Q000378:metabolism; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000187:drug effects* / Q000473:pathology; D018890:Chemoprevention / Q000379:methods; D003092:Colitis / Q000139:chemically induced / Q000150:complications / Q000473:pathology*; D003106:Colon / Q000187:drug effects / Q000473:pathology; D015179:Colorectal Neoplasms / Q000150:complications / Q000473:pathology / Q000517:prevention & control*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016264:Dextran Sulfate / Q000009:adverse effects; D019587:Dietary Supplements; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005973:Glutamine / Q000008:administration & dosage*; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D012007:Rectum / Q000187:drug effects / Q000473:pathology; D012720:Severity of Illness Index
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D014408:Biomarkers, Tumor; D016328:NF-kappa B; D005973:Glutamine; D016264:Dextran Sulfate; D052247:Nitric Oxide Synthase Type II; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D001397:Azoxymethane