Resveratrol induces pro-apoptotic endoplasmic reticulum stress in human colon cancer cells.
Resveratrol (3,4',5 tri-hydroxystilbene), a naturally occurring polyphenolic compound highly enriched 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, was measured by FACS analysis. Treatment of HT29 human colon carcinoma cells with resveratrol was found to induce a number of signature ER stress markers; phosphorylation of eukaryotic initiation factor-2alpha (eIF-2alpha), ER stress-specific XBP1 splicing and CCAAT/enhancer-binding protein-homologous protein (CHOP). In addition, resveratrol induced up-regulation of glucose-regulated protein (GRP)-78, suggesting the induction of ER stress. Furthermore, the inhibition of caspase-4 activity by z-LEVD-fmk significantly reduced resveratrol-induced apoptosis. Taken together, the present study therefore provides strong evidence to support an important role of ER stress response in mediating the resveratrol-induced apoptosis.
Park
Jong-Wook
JW
Department of Immunology and Chronic Disease Research Center and Institute for Medical Science, School of Medicine, Keimyung University, 194 DingSan-Dong Jung-Gu, Taegu 700-712, South Korea.
Woo
Kyung Jin
KJ
Lee
Jung-Tae
JT
Lim
Jun Hee
JH
Lee
Tae-Jin
TJ
Kim
Sang Hyun
SH
Choi
Yung Hyun
YH
Kwon
Taeg Kyu
TK
D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D020169:Caspases / Q000378:metabolism; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics; D004721:Endoplasmic Reticulum / Q000187:drug effects* / Q000378:metabolism; D000091342:Endoplasmic Reticulum Chaperone BiP; D015852:Eukaryotic Initiation Factor-2 / Q000235:genetics / Q000378:metabolism; D005434:Flow Cytometry; D019073:HT29 Cells / Q000187:drug effects; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics; D010766:Phosphorylation / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D000071701:Regulatory Factor X Transcription Factors; D000077185:Resveratrol; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013267:Stilbenes / Q000494:pharmacology*; D051742:Transcription Factor CHOP / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors; D000071717:X-Box Binding Protein 1
D016588:Anticarcinogenic Agents; D004268:DNA-Binding Proteins; D000091342:Endoplasmic Reticulum Chaperone BiP; D015852:Eukaryotic Initiation Factor-2; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D009687:Nuclear Proteins; D012333:RNA, Messenger; D000071701:Regulatory Factor X Transcription Factors; D013267:Stilbenes; D014157:Transcription Factors; D000071717:X-Box Binding Protein 1; C000605543:XBP1 protein, human; D051742:Transcription Factor CHOP; D020169:Caspases; D000077185:Resveratrol