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      Resveratrol and cancer: focus on in vivo evidence

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          Abstract

          Resveratrol is a naturally occurring polyphenol that provides a number of anti-aging health benefits including improved metabolism, cardioprotection, and cancer prevention. Much of the work on resveratrol and cancer comes from in vitro studies looking at resveratrol actions on cancer cells and pathways. There are, however, comparatively fewer studies that have investigated resveratrol treatment and cancer outcomes in vivo, perhaps limited by its poor bioavailability when taken orally. Although research in cell culture has shown promising and positive effects of resveratrol, evidence from rodents and humans is inconsistent. This review highlights the in vivo effects of resveratrol treatment on breast, colorectal, liver, pancreatic, and prostate cancers. Resveratrol supplementation in animal models of cancer has shown positive, neutral as well as negative outcomes depending on resveratrol route of administration, dose, tumor model, species, and other factors. Within a specific cancer type, there is variability between studies with respect to strain, age, and sex of animal used, timing and method of resveratrol supplementation, and dose of resveratrol used to study cancer endpoints. Together, the data suggest that many factors need to be considered before resveratrol can be used for human cancer prevention or therapy.

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          Most cited references123

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          High absorption but very low bioavailability of oral resveratrol in humans.

          The dietary polyphenol resveratrol has been shown to have chemopreventive activity against cardiovascular disease and a variety of cancers in model systems, but it is not clear whether the drug reaches the proposed sites of action in vivo after oral ingestion, especially in humans. In this study, we examined the absorption, bioavailability, and metabolism of 14C-resveratrol after oral and i.v. doses in six human volunteers. The absorption of a dietary relevant 25-mg oral dose was at least 70%, with peak plasma levels of resveratrol and metabolites of 491 +/- 90 ng/ml (about 2 microM) and a plasma half-life of 9.2 +/- 0.6 h. However, only trace amounts of unchanged resveratrol (<5 ng/ml) could be detected in plasma. Most of the oral dose was recovered in urine, and liquid chromatography/mass spectrometry analysis identified three metabolic pathways, i.e., sulfate and glucuronic acid conjugation of the phenolic groups and, interestingly, hydrogenation of the aliphatic double bond, the latter likely produced by the intestinal microflora. Extremely rapid sulfate conjugation by the intestine/liver appears to be the rate-limiting step in resveratrol's bioavailability. Although the systemic bioavailability of resveratrol is very low, accumulation of resveratrol in epithelial cells along the aerodigestive tract and potentially active resveratrol metabolites may still produce cancer-preventive and other effects.
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            Plant foods and herbal sources of resveratrol.

            Stilbenes, in particular trans-resveratrol and its glucoside, are widely reported to be beneficial to health, having been shown to possess antioxidative, anticarcinogenic, and antitumor properties. Major dietary sources include grapes, wine, peanuts, and soy; however, they can also be introduced into the diet through Itadori tea, which has long been used in Japan and China as a traditional herbal remedy for heart disease and strokes. Analysis of grapes, peanuts, and Itadori tea shows that they contain mainly trans-resveratrol glucoside. In contrast, red wines are primarily a source of the aglycones cis- and trans-resveratrol. While peanuts and grapes contain low levels of the stilbenes, Itadori tea and red wine both supply relatively high concentrations of resveratrol. For people who do not consume alcohol, Itadori tea may be a suitable substitute for red wine. However, further study on the potential biological effects of other endogenous compounds in Itadori tea is required and there is also a need for more information on the absorption and in vivo biomedical actions of free and conjugated resveratrol.
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              Epidemiology of hepatitis C virus infection.

              Globally, hepatitis C virus (HCV) has infected an estimated 130 million people, most of whom are chronically infected. HCV-infected people serve as a reservoir for transmission to others and are at risk for developing chronic liver disease, cirrhosis, and primary hepatocellular carcinoma (HCC). It has been estimated that HCV accounts for 27% of cirrhosis and 25% of HCC worldwide. HCV infection has likely been endemic in many populations for centuries. However, the wave of increased HCV-related morbidity and mortality that we are now facing is the result of an unprecedented increase in the spread of HCV during the 20th century. Two 20th century events appear to be responsible for this increase; the widespread availability of injectable therapies and the illicit use of injectable drugs.
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                Author and article information

                Journal
                Endocr Relat Cancer
                Endocr. Relat. Cancer
                ERC
                Endocrine-Related Cancer
                Bioscientifica Ltd (Bristol )
                1351-0088
                1479-6821
                June 2014
                5 February 2014
                : 21
                : 3
                : R209-R225
                Affiliations
                [1]Graduate Center for Nutritional Sciences, Markey Cancer Center, University of Kentucky College of Medicine Wethington Building, Room 591, 900 South Limestone, Lexington, Kentucky, 40536-0200USA
                [1 ]Department of Pediatrics Graduate Center for Toxicology, Markey Cancer Center, University of Kentucky College of Medicine Lexington, Kentucky, 40536-0096USA
                Author notes
                Correspondence should be addressed to K J Pearson; Email: kevin.pearson@ 123456uky.edu
                Article
                ERC130171
                10.1530/ERC-13-0171
                4013237
                24500760
                438933d8-8a8f-4f29-9777-4044e5b00886
                © 2014 The authors

                This work is licensed under a Creative Commons Attribution 3.0 Unported License

                History
                : 3 February 2014
                : 5 February 2014
                Categories
                Review

                Oncology & Radiotherapy
                colon,mammary gland,obesity,phytoestrogen,prostate
                Oncology & Radiotherapy
                colon, mammary gland, obesity, phytoestrogen, prostate

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