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5-aminosalicylic acid mediates expression of cyclooxygenase-2 and 15-hydroxyprostaglandin dehydrogenase to suppress colorectal tumorigenesis. 2012

Jun Miyoshi, and Tomoharu Yajima, and Katsuyoshi Shimamura, and Katsuyoshi Matsuoka, and Susumu Okamoto, and Hajime Higuchi, and Shinsuke Funakoshi, and Hiromasa Takaishi, and Toshifumi Hibi
Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.

BACKGROUND Cyclooxygenase-2 (COX-2) is a key enzyme that produces prostaglandin E2 (PGE2) and plays an important role in colorectal tumor growth. In addition, recent researches focused on 15-hydroxyprostaglandin dehydrogenase (15-PGDH), which degrades PGE2. Here we determined the effect of 5-aminosalicylic acid (5-ASA) on COX-2 and 15-PGDH expression and investigated its preventive effect for colorectal cancer (CRC). METHODS HT-29 cells were used in the in vitro experiments. c-Ha-ras transgenic mice were employed in order to explore the chemopreventive effects. Western blotting analysis was performed and the protein expression of COX-2 and 15-PGDH was quantified. RESULTS 5-ASA significantly suppressed COX-2 expression and induced 15-PGDH expression in HT-29 cells. In the transgenic mice, oral 5-ASA intake reduced the incidence of colorectal tumor formation and the tumor size. Furthermore, we observed a down-regulation of COX-2 and an up-regulation of 15-PGDH in the tissue from colons of these mice. CONCLUSIONS 5-ASA exerts a preventive effect against colorectal tumor development through mediation of COX-2 and 15-PGDH expression.

UI MeSH Term Description Entries
D008810 Mice, Inbred C57BL One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases. Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D008822 Mice, Transgenic Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN. Transgenic Mice,Founder Mice, Transgenic,Mouse, Founder, Transgenic,Mouse, Transgenic,Mice, Transgenic Founder,Transgenic Founder Mice,Transgenic Mouse
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D006911 Hydroxyprostaglandin Dehydrogenases Catalyzes reversibly the oxidation of hydroxyl groups of prostaglandins. Hydroxyprostaglandin Dehydrogenase,Prostacyclin Dehydrogenase,Dehydrogenase, Hydroxyprostaglandin,Dehydrogenase, Prostacyclin,Dehydrogenases, Hydroxyprostaglandin
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D015179 Colorectal Neoplasms Tumors or cancer of the COLON or the RECTUM or both. Risk factors for colorectal cancer include chronic ULCERATIVE COLITIS; FAMILIAL POLYPOSIS COLI; exposure to ASBESTOS; and irradiation of the CERVIX UTERI. Colorectal Cancer,Colorectal Carcinoma,Colorectal Tumors,Neoplasms, Colorectal,Cancer, Colorectal,Cancers, Colorectal,Carcinoma, Colorectal,Carcinomas, Colorectal,Colorectal Cancers,Colorectal Carcinomas,Colorectal Neoplasm,Colorectal Tumor,Neoplasm, Colorectal,Tumor, Colorectal,Tumors, Colorectal
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D051546 Cyclooxygenase 2 An inducibly-expressed subtype of prostaglandin-endoperoxide synthase. It plays an important role in many cellular processes and INFLAMMATION. It is the target of COX2 INHIBITORS. COX-2 Prostaglandin Synthase,Cyclo-Oxygenase II,Cyclooxygenase-2,PGHS-2,PTGS2,Prostaglandin H Synthase-2,COX 2 Prostaglandin Synthase,Cyclo Oxygenase II,Prostaglandin H Synthase 2,Prostaglandin Synthase, COX-2,Synthase, COX-2 Prostaglandin
D019073 HT29 Cells Human colonic ADENOCARCINOMA cells that are able to express differentiation features characteristic of mature intestinal cells such as the GOBLET CELLS. HT-29 Cells,Cell, HT-29,Cell, HT29,Cells, HT-29,Cells, HT29,HT 29 Cells,HT-29 Cell,HT29 Cell
D019804 Mesalamine An anti-inflammatory agent, structurally related to the SALICYLATES, which is active in INFLAMMATORY BOWEL DISEASE. It is considered to be the active moiety of SULPHASALAZINE. (From Martindale, The Extra Pharmacopoeia, 30th ed) 5-Aminosalicylate,Mesalazine,5-Aminosalicylic Acid,Asacol,Asacolon,Ascolitin,Canasa,Claversal,Fivasa,Lixacol,Mesalamine Hydrochloride,Mesalamine Monosodium Salt,Mesasal,Novo-5 ASA,Pentasa,Rowasa,Salofalk,m-Aminosalicylic Acid,meta-Aminosalicylic Acid,5 Aminosalicylate,5 Aminosalicylic Acid,Hydrochloride, Mesalamine,Monosodium Salt, Mesalamine,Novo 5 ASA,m Aminosalicylic Acid,meta Aminosalicylic Acid

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