DA-6034, a derivative of flavonoid, prevents and ameliorates dextran sulfate sodium-induced colitis and inhibits colon carcinogenesis
- Authors
- Nam, Su Youn; Kim, Joo Sung; Kim, Jung Mogg; Lee, Jong Yeul; Kim, Nayoung; Jung, Hyun Chae; Song, In Sung
- Issue Date
- Feb-2008
- Publisher
- SAGE PUBLICATIONS LTD
- Keywords
- DA-6034; inflammatory bowel disease; colon cancer
- Citation
- EXPERIMENTAL BIOLOGY AND MEDICINE, v.233, no.2, pp.180 - 191
- Indexed
- SCIE
SCOPUS
- Journal Title
- EXPERIMENTAL BIOLOGY AND MEDICINE
- Volume
- 233
- Number
- 2
- Start Page
- 180
- End Page
- 191
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/172138
- DOI
- 10.3181/0707-RM-186
- ISSN
- 1535-3702
- Abstract
- Previously, we have shown that DA-6034, a synthetic derivative of flavonoid eupatilin, inhibited NF-kappa B 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-kappa B kinase alpha (IKK alpha), 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-IKK alpha 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.
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