Resveratrol as an anticancer nutrient: molecular basis, open questions and promises.
The polyphenol resveratrol is an anticancer nutrient that was shown to inhibit cancer initiation and promotion [Jang M, Cai L, Udeani GO, Slowing KV, Thomas CF, Beecher CW, et al. Cancer chemopreventive activity of resveratrol, a natural product derived from grapes. Science 1997;275:218-20]. The absorption, transport and metabolism of resveratrol will be reviewed as well as its actions in multiple pathways involved in the regulation of the cell cycle and the induction of apoptosis. Resveratrol acts as a selective estrogen receptor modulator (SERM) and regulates proteins involved in DNA synthesis and cell cycle, such as p(53) and Rb/E2F, cyclins, cyclin-dependent kinases (CDKs) and their inhibitors. Resveratrol affects the activity of transcriptional factors involved in proliferation and stress responses, such as NF-kB, AP1 and Egr1. Part of these events is mediated by mitogen-activated protein kinases (MAPKs) and tyrosine kinases (e.g., Src) and leads to the modulation of survival and apoptotic factors [e.g., Bcl2 family members, inhibitors of apoptosis (IAPs), ceramide] as well as enzymes involved in carcinogenesis [cyclooxygenases (COXs), nitric oxide synthase (NOS), phase I and II enzymes]. Moreover, resveratrol affects the expression and the activity of cotranscriptional factors such as p(300) and sirtuin 1. Thus, resveratrol potential as an anticancer chemopreventive and chemotherapeutic agent and its implication in the prosurvival versus prodeath pathway induction will be discussed.
Signorelli
Paola
P
Laboratory of Biochemistry and Molecular Biology, San Paolo University Hospital, School of Medicine, University of Milan, 20142 Milan, Italy.
Ghidoni
Riccardo
R
D000818:Animals; D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use; D000975:Antioxidants / Q000494:pharmacology; D018797:Cell Cycle Proteins / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D004032:Diet; D006801:Humans; D019001:Nitric Oxide Synthase / Q000187:drug effects; D010636:Phenols / Q000627:therapeutic use*; D048789:Phytoestrogens / Q000627:therapeutic use; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects; D000077185:Resveratrol; D015398:Signal Transduction / Q000187:drug effects; D013107:Sphingolipids / Q000502:physiology; D013267:Stilbenes / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*
D016588:Anticarcinogenic Agents; D000972:Antineoplastic Agents, Phytogenic; D000975:Antioxidants; D018797:Cell Cycle Proteins; D010636:Phenols; D048789:Phytoestrogens; D013107:Sphingolipids; D013267:Stilbenes; D019001:Nitric Oxide Synthase; D011451:Prostaglandin-Endoperoxide Synthases; D000077185:Resveratrol