title: Elevated gadd153/chop expression during resveratrol-induced apoptosis in human colon cancer cells.
abstract: Resveratrol (3,4',5-tri-hydroxystilbene), a natural phytoalexin found at high levels in grapes and red wine, has been shown to induce anti-proliferation and apoptosis of human cancer cell lines. Resveratrol-induced dose-dependent apoptotic cell death in colon carcinoma cells, as measured by FACS analysis and internucleosomal DNA fragmentation assays. We demonstrate for the first time that resveratrol induce CCAAT/enhancer-binding protein-homologous protein (CHOP). Resveratrol-induced CHOP mRNA (and also protein) expression was inhibited by JNK specific inhibitor, but not ERK, p38 MAPK, PI3K and NF-kappaB inhibitors. Resveratrol-induced expression of CHOP involves the putative Sp1 site within the CHOP promoter region. Using a combination of the Sp1 cDNA transfection, the luciferase reporter assay and Sp1 inhibitor assay, we found that Sp1 site is required for resveratrol-mediated activation of the CHOP promoter. Suppression of CHOP expression by CHOP siRNA and treatment with mithramycin A attenuated resveratrol-induced apoptosis. Taken together, the present studies suggest that induction of CHOP protein may be involved, at least in part, in resveratrol-induced apoptosis.
authors.affiliation: Department of Immunology, School of Medicine, Keimyung University, 194 DongSan-Dong Jung-Gu, Taegu 700-712, South Korea.
authors.forename: Kyung Jin
authors.initials: KJ
authors.lastname: Woo
authors.forename: Tae Jin
authors.initials: TJ
authors.lastname: Lee
authors.forename: Sang Han
authors.initials: SH
authors.lastname: Lee
authors.forename: Jin-Man
authors.initials: JM
authors.lastname: Lee
authors.forename: Ji-Hyung
authors.initials: JH
authors.lastname: Seo
authors.forename: Yong-Jin
authors.initials: YJ
authors.lastname: Jeong
authors.forename: Jong-Wook
authors.initials: JW
authors.lastname: Park
authors.forename: Taeg Kyu
authors.initials: TK
authors.lastname: Kwon
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D003110:Colonic Neoplasms / Q000235:genetics* / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D019073:HT29 Cells; D006801:Humans; D020935:MAP Kinase Signaling System; D034741:RNA, Small Interfering; D000077185:Resveratrol; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013267:Stilbenes / Q000494:pharmacology*; D051742:Transcription Factor CHOP / Q000235:genetics*; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: C497249:DDIT3 protein, human; D034741:RNA, Small Interfering; D013267:Stilbenes; D051742:Transcription Factor CHOP; D000077185:Resveratrol