Chemoprevention of cancer and cardiovascular disease by resveratrol.
Resveratrol (trans-3,4',5-trihydroxystibene) is a phytopolyphenol isolated from the seeds and skins of grapes. Recent studies indicate that resveratrol can block the process of multistep carcinogenesis, namely, tumor initiation, promotion and progression. Resveratrol can also reduce the risk of cardiovascular disease in man. The molecular mechanisms of resveratrol in chemoprevention of cancer and cardiovascular disease are interesting and under intensive investigation. Resveratrol was found to strongly inhibit nitric oxide (NO) generation in activated macrophages, as measured by the amount of nitrite released into the culture medium, and resveratrol strongly reduced the amount of cytosolic inducible nitric oxide synthase (iNOS) protein. The activation of nuclear factor kappa B (NF kappa B) induced by lipopolysaccharide (LPS) was inhibited by resveratrol. The phosphorylation and degradation of nuclear factor inhibitor kappa B alpha (I kappa B alpha) were inhibited by resveratrol simultaneously. Reactive oxygen species (ROS) are regarded as having carcinogenic potential and have been associated with tumor promotion. Resveratrol may act as a reactive oxygen species scavenger to suppress tumor development. In addition, resveratrol may block multistep carcinogenesis through mitotic signal transduction blockade. Reactive oxygen species are pivotal factors in the genesis of heart disease. Meanwhile, efficient endogenous antioxidants, including superoxide dismutase (SOD), glutathione peroxidase (GSHPx), and catalase, are present in tissues. A fine balance between reactive oxygen species and endogenous antioxidants is believed to exist. Any disturbance of this balance in favor of reactive oxygen species causes an increase in oxidative stress and initiates subcellular changes, leading to cardiomyopathy and heart failure. The experimental results indicate that exogenous antioxidant resveratrol is of value in chemopreventing the development of heart disease. It is urgent that more efforts be made to investigate newer therapies employing antioxidants for the chemoprevention of cardiovascular disease and cancer.
Lin
J K
JK
Institute of Biochemistry, College of Medicine, National Taiwan University, Taipei, R.O.C.
Tsai
S H
SH
D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D002273:Carcinogens / Q000494:pharmacology; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000517:prevention & control*; D002453:Cell Cycle / Q000187:drug effects; D019938:Cyclin D1 / Q000037:antagonists & inhibitors; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D005786:Gene Expression Regulation / Q000187:drug effects; D006133:Growth Substances / Q000494:pharmacology; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D009369:Neoplasms / Q000453:epidemiology / Q000517:prevention & control*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D052247:Nitric Oxide Synthase Type II; D018384:Oxidative Stress; D010766:Phosphorylation / Q000187:drug effects; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D017382:Reactive Oxygen Species; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D000077185:Resveratrol; D012307:Risk Factors; D019685:Rosales; D015398:Signal Transduction / Q000187:drug effects; D013267:Stilbenes / Q000494:pharmacology / Q000627:therapeutic use*; D014158:Transcription, Genetic / Q000187:drug effects; D014920:Wine
D016588:Anticarcinogenic Agents; D002273:Carcinogens; D004791:Enzyme Inhibitors; D006133:Growth Substances; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D013267:Stilbenes; D019938:Cyclin D1; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D020794:Receptor Protein-Tyrosine Kinases; D000077185:Resveratrol