Elevated gadd153/chop expression during resveratrol-induced apoptosis in human colon cancer cells.
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.
Woo
Kyung Jin
KJ
Department of Immunology, School of Medicine, Keimyung University, 194 DongSan-Dong Jung-Gu, Taegu 700-712, South Korea.
Lee
Tae Jin
TJ
Lee
Sang Han
SH
Lee
Jin-Man
JM
Seo
Ji-Hyung
JH
Jeong
Yong-Jin
YJ
Park
Jong-Wook
JW
Kwon
Taeg Kyu
TK
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
C497249:DDIT3 protein, human; D034741:RNA, Small Interfering; D013267:Stilbenes; D051742:Transcription Factor CHOP; D000077185:Resveratrol