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.