title: Suppression of promoter-dependent transcriptional activity of inducible nitric oxide synthase by sodium butyrate in colon cancer cells.
abstract: Butyrate suppresses the growth of colon cancer cells, inducing differentiation and apoptosis in vitro. Increased expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) has been suggested to be closely involved in colon carcinogenesis. In this study, effects of sodium butyrate on the promoter-dependent transcriptional activity of iNOS and COX-2 genes were investigated in a colon cancer cell line, DLD-1, using a reporter gene assay system. Sodium butyrate significantly reduced promoter-dependent iNOS transcriptional activity dose-dependently at concentrations higher than 0.1 mM. COX-2 transcriptional activity was not suppressed, but slightly increased. While hyperacetylated histones appeared at concentrations of sodium butyrate suppressing iNOS gene promoter activity, promoter-dependent transcriptional activities of iNOS and COX-2 genes were both increased by the histone deacetylase inhibitor trichostatin A. These results suggested that sodium butyrate exhibits differential effects on iNOS and COX-2 genes, acting to suppress iNOS expression via mechanisms independent of histone acetylation.
authors.affiliation: Cancer Prevention Division, National Cancer Center Research Institute, 1-1 Tsukiji 5-chome, Chuo-ku, Tokyo 104-0045, Japan.
authors.forename: Yasuyoshi
authors.initials: Y
authors.lastname: Sasahara
authors.forename: Michihiro
authors.initials: M
authors.lastname: Mutoh
authors.forename: Mami
authors.initials: M
authors.lastname: Takahashi
authors.forename: Kazunori
authors.initials: K
authors.lastname: Fukuda
authors.forename: Naomi
authors.initials: N
authors.lastname: Tanaka
authors.forename: Takashi
authors.initials: T
authors.lastname: Sugimura
authors.forename: Keiji
authors.initials: K
authors.lastname: Wakabayashi
mesh_terms: D002087:Butyrates / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D003110:Colonic Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D006801:Humans; D019001:Nitric Oxide Synthase / Q000096:biosynthesis* / Q000235:genetics*; D052247:Nitric Oxide Synthase Type II; D011401:Promoter Regions, Genetic / Q000187:drug effects / Q000235:genetics; D015533:Transcriptional Activation / Q000187:drug effects; D014407:Tumor Cells, Cultured
chemical_list: D002087:Butyrates; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II