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Elevated gadd153/chop expression during resveratrol-induced apoptosis in human colon cancer cells

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Author(s)
Kyung Jin WooTae Jin LeeSang Han LeeJin-Man LeeJi-Hyung SeoYong-Jin JeongJong-Wook ParkTaeg Kyu Kwon
Publication Year
2007
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-κB 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.

Keywords
Resveratrol;
CHOP;
GADD153;
Apoptosis;
Sp1;
Promoter;
Colon cancer
Department
Dept. of Immunology (면역학)
Publisher
School of Medicine
Citation
Biochemical Pharmacology, Vol.73(1) : 68-76, 2007
Type
Article
ISSN
0006-2952
DOI
10.1016/j.bcp.2006.09.015
URI
http://kumel.medlib.dsmc.or.kr/handle/2015.oak/35184
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