Resveratrol and cancer: focus on in vivo evidence

Lindsay G Carter,John A D'Orazio,Kevin J Pearson

doi:10.1530/erc-13-0171

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.

Highlights

Resveratrol is a phytoalexin found in many plant species, including those often consumed by humans such as grapes, peanuts, and berries; it is produced in plants in response to mechanical injury, fungal infection, and u.v. radiation (Langcake & Pryce 1976)
The highest naturally occurring levels of resveratrol are found in Polygonum cuspidatum ( Japanese knotweed), a plant which has been used for hundreds of years in traditional Asian medicine to treat inflammation and other ailments (Vastano et al 2000, Burns et al 2002)
Q 2014 The authors Printed in Great Britain azoxymethane to induce colon tumorigenesis in 8-weekold male Fisher 344 rats, Tessitore et al (2000) found that resveratrol supplementation in drinking water for 100 days decreased the appearance of aberrant crypt foci (ACF) precursors for colon cancer compared with rats receiving control water

Summary

Introduction

Resveratrol (trans-3,5,40-trihydroxystilbene) is a phytoalexin found in many plant species, including those often consumed by humans such as grapes, peanuts, and berries; it is produced in plants in response to mechanical injury, fungal infection, and u.v. radiation (Langcake & Pryce 1976). Later studies found that in mouse models of skin tumorigenesis, topical resveratrol prevented tumor formation by promoting apoptosis, regulating the cell cycle, and inhibiting COX activity and prostaglandin production (Afaq et al 2003, Reagan-Shaw et al 2004, Kalra et al 2008). Resveratrol supplementation was shown to decrease cellular proliferation by 5% in colorectal cancer tissue, as assessed by Ki67 staining (Patel et al 2010) Since there is such rapid conjugation and low bioavailability of resveratrol, the in vivo use of resveratrol for cancer prevention and treatment is uncertain. Resveratrol and grape powder administration had no effect on cancerous mucosa Wnt signaling, but their supplementation resulted in decreased Wnt target gene expression in normal mucosa (effects of all treatment groups combined). The most significant effects were observed with the low-dose

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Discussion

Conclusion