摘要
Resveratrol is a naturally occurring stilbene with desirable cardioprotective and anti-cancer properties. We have demonstrated the existence of a plasma membrane receptor for resveratrol near the arginine-glycine-aspartate (RGD) recognition site on integrin α vβ 3 that is involved in stilbene-induced apoptosis of cancer cells. Resveratrol treatment in vitro causes activation and nuclear translocation of mitogen-activated protein kinase (ERK1/2), consequent phosphorylation of Ser-15 of p53, and apoptosis. An RGD peptide blocks these actions of resveratrol. By a PD98059-inhibitable process, resveratrol causes inducible COX-2 to accumulate in the nucleus where it complexes with pERK1/2 and p53. Chromatin immunoprecipitation reveals binding of nuclear COX-2 to promoters of certain p53-responsive genes, including PIG3 and Bax. NS-398, a specific pharmacologic inhibitor of COX-2, prevents resveratrol-induced complexing of nuclear ERK1/2 with COX-2 and with pSer-15-p53 and subsequent apoptosis; cyclooxygenase enzyme activity is not involved. Molecular steps in the pro-apoptotic action of resveratrol in cancer cells include induction of intranuclear COX-2 accumulation relevant to activation of p53. Epidermal growth factor, estrogen, and thyroid hormone act downstream of ERK1/2 to prevent resveratrol-induced apoptosis.
原文 | 英語 |
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頁(從 - 到) | 79-88 |
頁數 | 10 |
期刊 | Annals of the New York Academy of Sciences |
卷 | 1215 |
發行號 | 1 |
DOIs | |
出版狀態 | 已發佈 - 1月 2011 |
對外發佈 | 是 |
ASJC Scopus subject areas
- 神經科學 (全部)
- 生物化學、遺傳與分子生物學 (全部)
- 科學史與哲學