Anticancer Effects of Resveratrol

Clinical chemoprevention involves the use of pharmacological or natural agents to prevent the development of cancer in high-risk individuals.  These agents must have the ability to reverse or arrest the progression of premalignant lesions into invasive cancer.  However, unlike cytotoxic agents, which are used in chemotherapy, chemoprevention agents must have relatively few side effects and they are intended for long-term daily use by cancer-susceptible individuals who are otherwise healthy.  The clinical evaluation of these agents requires large numbers of participants and a lengthy treatment course, and there are often difficulties with trial recruitment, compliance, and cost.  Thus protein or other types of biomarkers are often desirable, because they can facilitate the conduct of these trials by serving as intermediate surrogate endpoints. 

Resveratrol is a naturally occurring phytochemical found in approximately 72 plant species, including food products like grapes, peanuts, and various herbs.  While red wine and grapes are probably its main sources in western diets, one of its richest sources is the herb Polygonum cuspidatum, which has been used in Asian folk medicine.  Resveratrol is currently being evaluated in preclinical studies as a potential cancer chemoprevention agent.  It has previously been shown to have anticancer activities in both cell culture and animal carcinogenesis models of both hematological and solid tumors (1, 2).  Although it is widely available in the form of unregulated herbal supplements, there is relatively little clinical data characterizing either its efficacy or safety in the treatment or prevention of cancer.

Andrew K. Joe, M.D. is evaluating both pharmacological and natural agents for potential use as chemoprevention agents.  In human cancer cell lines, Dr. Joe is conducting assays using these compounds both to provide preclinical evidence of anticancer activity and to identify surrogate biomarkers for evaluating their in vivo treatment efficacy.  Results of such studies will facilitate evaluation of these compounds in clinical chemoprevention trials.  Dr. Joe has demonstrated that resveratrol has broad anticancer activity in a wide spectrum of human cancer cell lines of different tissue types, including esophageal and colorectal carcinoma cells, types of cancer in which resveratrol may have a role in chemoprevention (3, 4).  Resveratrol causes a dose-dependent cancer cell growth inhibition, and this antiproliferative effect appears to be due to its ability to induce S-phase arrest and apoptotic cell death.  Furthermore, several proteins involved in cell proliferation are inhibited after treatment, and assays for these proteins in biopsy samples might provide useful surrogate endpoints to evaluate treatment efficacy in large clinical trials.

Editor’s note:

Andrew K. Joe, M.D. is an Assistant Professor of Medicine at Columbia University College of Physicians and Surgeons.

1.  Jang, M., Cai, L., Udeani, G.O., Slowing, K.V., Thomas, C.F., Beecher, C.W., Fong, H.H., Farnsworth, N.R., Kinghorn, A.D., Mehta, R.G., Moon, R.C., and Pezzuto, J.M.  Cancer chemopreventive activity of resveratrol, a natural product derived from grapes.  Science.  1997, 275(5297): 218-20.

2.  Soleas, G.J., Diamandis, E.P., and Goldberg, D.M.  Resveratrol: a molecule whose time has come? And gone?  Clin Biochem.  1997, 30(2): 91-113.

3.  Joe, A.K., Liu, H., Vural, M.E., Xiao, D.H., Beer, D.G., Ting, W., and Weinstein, I.B.  Resveratrol inhibits growth, induces arrest at the S/G2 transition and apoptosis in several human cancer cell lines.  92nd Annual Meeting of the American Association for Cancer Research, New Orleans, LA, March 24-28, 2001.

4.  Antman, K., Benson, M.C., Chabot, J., Cobrinik, D., Grann, V.R., Jacobson, J.S., Joe, A.K., Katz, A.E., Kelly, K., Neugut, A.I., Russo, D., Tiersten, A., and Weinstein, I.B.  Complementary and alternative medicine: the role of the cancer center.  J Clin Oncol. 2001, 19 (Suppl 1): 55S-60S.