S-Space College of Medicine/School of Medicine (의과대학/대학원) Program in Clinical Pharmacology (협동과정-임상약리학전공) Journal Papers (저널논문_협동과정-임상약리학전공)
DA-6034, a derivative of flavonoid, prevents and ameliorates dextran sulfate sodium-induced colitis and inhibits colon carcinogenesis
- Nam, Su Youn; Kim, Joo Sung; Kim, Jung Mogg; Lee, Jong Yeul; Kim, Nayoung; Jung, Hyun Chae; Song, In Sung
- Issue Date
- Exp Biol Med (Maywood) 233:180-191, 2008
- Acute Disease; Animals; Apoptosis/drug effects; Body Weight/drug effects; Cell Transformation, Neoplastic; Colitis/*chemically induced/complications/enzymology/*prevention & control; Colonic Neoplasms/complications/pathology/*prevention & control; Cyclooxygenase 2/metabolism; Dextran Sulfate/*pharmacology; Disease Models, Animal; Flavonoids/*pharmacology; I-kappa B Kinase/metabolism; Ki-67 Antigen/metabolism; Male; Mice; Mice, Inbred C57BL; Phosphorylation/drug effects
- Previously, we have shown that DA-6034, a synthetic derivative of flavonoid eupatilin, inhibited NF-kappaB activation in colon epithelial cells and prevented trinitrobenzene sulfonic acid-induced rat colitis. The aim of this study was to investigate the preventive and therapeutic effect of DA-6034 on dextran sulfate sodium (DSS)-induced colitis and on inflammation-related cancer. C57BL/6 mice were given 4% DSS for 5 days with and without DA-6034 in the acute preventive model. In the acute therapeutic model, mice were given 4% DSS for 5 days followed by rectal administration of DA-6034. Colitis was quantified by body weight, disease activity index (DAI), colon length, and histology. In the inflammation-related cancer model, mice were given a single intraperitoneal injection of azoxymethane, then three cycles of 2% DSS for 5 days, then 2 weeks of free water consumption. Apoptosis was determined by in situ terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling assay, and the expression of Ki-67, phospho-kappaB kinase alpha (IKKalpha), and COX-2 were evaluated by immunohistochemistry. In both the acute preventive and acute therapeutic models, DA-6034 significantly attenuated DSS-induced weight loss, an increase in DAI, and a shortening of colon length. DA-6034-treated mice maintained crypt architecture and revealed a scanty infiltration of inflammatory cells in both the preventive and therapeutic models. In the inflammation-related cancer model, DA-6034 reduced the number of colon tumors and ameliorated weight loss and shortening of colon length. DA-6034 strongly enhanced apoptosis and inhibited the expression of COX-2 and phospho-IKKalpha in inflammation-related colon cancer models. Our results suggest that DA-6034 prevents acute murine colitis and inhibits inflammation-related colon carcinogenesis. DA-6034 could be a potential therapeutic agent for inflammatory bowel disease.
- 1535-3702 (Print)
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