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DA-6034, a derivative of flavonoid, prevents and ameliorates dextran sulfate sodium-induced colitis and inhibits colon carcinogenesis

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dc.contributor.authorNam, Su Youn-
dc.contributor.authorKim, Joo Sung-
dc.contributor.authorKim, Jung Mogg-
dc.contributor.authorLee, Jong Yeul-
dc.contributor.authorKim, Nayoung-
dc.contributor.authorJung, Hyun Chae-
dc.contributor.authorSong, In Sung-
dc.date.accessioned2010-06-28-
dc.date.available2010-06-28-
dc.date.issued2008-01-29-
dc.identifier.citationExp Biol Med (Maywood). 233(2):180-191en
dc.identifier.issn1535-3702 (Print)-
dc.identifier.urihttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18222973-
dc.identifier.urihttp://www.ebmonline.org/cgi/reprint/233/2/180.pdf-
dc.identifier.urihttp://hdl.handle.net/10371/67866-
dc.description.abstractPreviously, 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.en
dc.language.isoenen
dc.publisherSociety for Experimental Biology and Medicineen
dc.subjectAcute Diseaseen
dc.subjectAnimalsen
dc.subjectApoptosis/drug effectsen
dc.subjectBody Weight/drug effectsen
dc.subjectCell Transformation, Neoplasticen
dc.subjectColitis/*chemically induced/complications/enzymology/*prevention & controlen
dc.subjectColonic Neoplasms/complications/pathology/*prevention & controlen
dc.subjectCyclooxygenase 2/metabolismen
dc.subjectDextran Sulfate/*pharmacologyen
dc.subjectDisease Models, Animalen
dc.subjectFlavonoids/*pharmacologyen
dc.subjectI-kappa B Kinase/metabolismen
dc.subjectKi-67 Antigen/metabolismen
dc.subjectMaleen
dc.subjectMiceen
dc.subjectMice, Inbred C57BLen
dc.subjectPhosphorylation/drug effectsen
dc.titleDA-6034, a derivative of flavonoid, prevents and ameliorates dextran sulfate sodium-induced colitis and inhibits colon carcinogenesisen
dc.typeArticleen
dc.contributor.AlternativeAuthor남수연-
dc.contributor.AlternativeAuthor김주성-
dc.contributor.AlternativeAuthor김정목-
dc.contributor.AlternativeAuthor이종열-
dc.contributor.AlternativeAuthor김나영-
dc.contributor.AlternativeAuthor정현채-
dc.contributor.AlternativeAuthor송인성-
dc.identifier.doi10.3181/0707-RM-186-
Appears in Collections:
College of Medicine/School of Medicine (의과대학/대학원)Internal Medicine (내과학전공)Journal Papers (저널논문_내과학전공)
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