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

Article Details

Citation

Copy to clipboard

Woo KJ, Lee TJ, Lee SH, Lee JM, Seo JH, Jeong YJ, Park JW, Kwon TK

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

Biochem Pharmacol. 2007 Jan 1;73(1):68-76. Epub 2006 Sep 19.

PubMed ID

17049495 [ View in PubMed

]

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.