Suppression of promoter-dependent transcriptional activity of inducible nitric oxide synthase by sodium butyrate in colon cancer cells.
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.
Sasahara
Yasuyoshi
Y
Cancer Prevention Division, National Cancer Center Research Institute, 1-1 Tsukiji 5-chome, Chuo-ku, Tokyo 104-0045, Japan.
Mutoh
Michihiro
M
Takahashi
Mami
M
Fukuda
Kazunori
K
Tanaka
Naomi
N
Sugimura
Takashi
T
Wakabayashi
Keiji
K
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
D002087:Butyrates; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II