Journal
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
Volume 486, Issue 2, Pages 95-102Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.abb.2009.01.018
Keywords
Resveratrol; Human cancer; Cell cycle regulation; Apoptosis; Transcription factors; Pro-oxidant; Lysosome; Growth signals
Categories
Funding
- NIH [R01 ES-015323, R01 CA-097249-01]
- [K01-AR048582-04]
- [R03 CA1 25855-01]
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Plant-derived polyphenolic compounds, such as the stilbene resveratrol (trans-3,4',5-trihydroxystilbene), have been identified as potent anti-cancer agents. Extensive in vitro studies revealed multiple intracellular targets of resveratrol, which affect cell growth, inflammation, apoptosis, angiogenesis, and invasion and metastasis. These include tumor suppressors p53 and Rb; cell cycle regulators, cyclins, CDKs, p21WAF1, p27KIP and INK and the checkpoint kinases ATM/ATR; transcription factors NF-kappa B, AP-1, c-Jun, and c-Fos; angiogenic and metastatic factors, VEGF and matrix metalloprotease 2/9; cyclooxygenases for inflammation; and apoptotic and survival regulators, Bax, Bak, PUMA, Noxa, TRAIL, APAF, survivin, Akt, Bcl2 and Bcl-X-L. In addition to its well-documented anti-oxidant properties, there is increasing evidence that resveratrol exhibits pro-oxidant activity under certain experimental conditions, causing oxidative DNA damage that may lead to cell cycle arrest or apoptosis. This review summarizes in vitro mechanistic data available for resveratrol and discusses new potential anti-cancer targets and the antiproliferative mechanisms of resveratrol. (C) 2009 Elsevier Inc. All rights reserved.
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