Resveratrol addiction: to die or not to die.
Resveratrol, a polyphenol derived from red grapes, berries, and peanuts, has been shown to mediate death of a wide variety of cells. The mechanisms by which resveratrol mediates cell death include necrosis, apoptosis, autophagy, and others. While most studies suggest that resveratrol kills tumor cells selectively, evidence is emerging that certain normal cells such as endothelial cells, lymphocytes, and chondrocytes are vulnerable to resveratrol. Cell killing by this stilbene may be mediated through any of numerous mechanisms that involve activation of mitochondria and of death caspases; upregulation of cyclin-dependent kinase inhibitors, tumor suppressor gene products, or death-inducing cytokines and cytokine receptors; or downregulation of cell survival proteins (survivin, cFLIP, cIAPs, X-linked inhibitor of apoptosis protein (XIAP), bcl-2, bcl-XL) or inhibition of cell survival kinases (e.g., mitogen-activiated protein kinases (MAPKs), AKT/phosphoinositide 3-kinase (PI3K), PKC, EGFR kinase) and survival transcription factors (nuclear factor-kappaB (NF-kappaB), activating protein 1 (AP-1), HIF-1alpha, signal transducer and activator of transcription (STAT3)). Induction of any of these pathways by resveratrol leads to cell death. While cell death is a hallmark of resveratrol, this polyphenol also has been linked with suppression of inflammation, arthritis, and cardiovascular diseases and delaying of aging. These attributes of resveratrol are discussed in detail in this review.
Shakibaei
Mehdi
M
Institute of Anatomy, Ludwig-Maximilian-University Munich, Munich, Germany.
Harikumar
Kuzhuvelil B
KB
Aggarwal
Bharat B
BB
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D016588:Anticarcinogenic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D002316:Cardiotonic Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D002453:Cell Cycle / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects*; D005638:Fruit; D006801:Humans; D011960:Receptors, Estrogen / Q000187:drug effects; D000077185:Resveratrol; D013267:Stilbenes / Q000009:adverse effects / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D019966:Substance-Related Disorders
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016588:Anticarcinogenic Agents; D002316:Cardiotonic Agents; D011960:Receptors, Estrogen; D013267:Stilbenes; D000077185:Resveratrol