Resveratrol, A Phytoalexin with a Multitude of Anti-Cancer Activities

Resveratrol is a polyphenol produced by certain plants in response to stress. A major dietary source of resveratrol is red wine. This polyphenol has a multitude of effects on mammalian cells, including inhibiting the proliferation and/or inducing apoptosis in cancer cells. This review focuses on recent insights into the metabolism, cancer-specific activities and molecular pathways of resveratrol action. While much work has been published on resveratrol’s effects on cancer cells in tissue culture, fewer studies have been performed with rodent cancer models. The animal work shows that resveratrol is effective in inhibiting the development or progression of tumors of the prostate, brain and esophagus. An interesting finding in an animal model of pancreatic cancer is the ability of resveratrol to not only inhibit tumor growth, but to also sensitize the tumor to gemcitabine. Analogous to other phytochemicals, resveratrol inhibits multiple signaling pathways including PI-3K/AKT, NF-kB, TGF-β and COX2 mediated signaling. The major metabolites of resveratrol include piceatannol, resveratrol glucuronide and monosulfated dihydroresveratrol. It is not clear if any of these metabolites have biological activity. There are currently three NCI-registered clinical trials with resveratrol. At present there are no published results from these trials. Low bioavailability of resveratrol may limit its in vivo effectiveness. Numerous questions remain to be answered regarding resveratrol’s biologic actions and its potential role in the chemoprevention and/or treatment of cancer.

Keywords: Angiogenesis, Apoptosis, Cancer, Cyclooxygenase, Diet, Food, Metastasis, NF-kB, Nutrition, Phase II enzymes, Phytoalexin, PI-3K/AKT, Resveratrol, SIRT-1, Tumor Progression.