Multiple molecular targets of resveratrol: Anti-carcinogenic mechanisms.
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-kappaB, 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.
Athar
Mohammad
M
Departments of Dermatology, Columbia University Medical Center, Irving Cancer Research Center, New York, NY 10032, USA.
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Jung Ho
JH
Kopelovich
Levy
L
Bickers
David R
DR
Kim
Arianna L
AL
D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy; D002403:Cathepsins / Q000187:drug effects / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D005260:Female; D006801:Humans; D007249:Inflammation / Q000517:prevention & control; D007938:Leukemia / Q000188:drug therapy; D008223:Lymphoma / Q000188:drug therapy; D008297:Male; D009369:Neoplasms / Q000188:drug therapy*; D011471:Prostatic Neoplasms / Q000188:drug therapy; D000077185:Resveratrol; D012449:Safety; D013267:Stilbenes / Q000627:therapeutic use*; D014157:Transcription Factors / Q000187:drug effects / Q000378:metabolism
D016588:Anticarcinogenic Agents; D013267:Stilbenes; D014157:Transcription Factors; D002403:Cathepsins; D000077185:Resveratrol