Editors' ChoiceCell Biology

Less resveratrol is more beneficial

Sci. Signal.  04 Aug 2015:
Vol. 8, Issue 388, pp. ec217
DOI: 10.1126/scisignal.aad1314

Resveratrol is a compound with potential health benefits found in red wine Cai et al. showed that a low rather than a high dose of resveratrol prevented tumor growth in mice and altered metabolic pathways in human tissues. The authors compared the dose-response curves of a dietary dose of resveratrol and a 200-fold higher amount in mice that spontaneously develop colorectal adenomas—precursors to cancer—that were fed a standard or a high-fat diet. In the mice on the high-fat diet, low-dose resveratrol reduced intestinal tumor development better than did the high dose. In mouse tumor cells, resveratrol efficacy was indicated by an increase in autophagy and senescence markers and activation of adenosine monophosphate (AMP)–activated protein kinase (AMPK)—an enzyme that functions in the maintenance of cellular energy homeostasis. Exposure of human colorectal cancer tissue to low concentrations of resveratrol also caused an increase in autophagy and activation of AMPK. Colorectal mucosal samples isolated from cancer patients who received a low-dose resveratrol regimen before tumor resection showed an increase in expression of the cytoprotective, oxidative stress-activated enzyme NAD(P)H dehydrogenase, quinone 1 (NQO1). These findings suggest that resveratrol operates by modulating energy balance and responding to stress.

H. Cai, E. Scott, A. Kholghi, C. Andreadi, A. Rufini, A. Karmokar, R. G. Britton, E. Horner-Glister, P. Greaves, D. Jawad, M. James, L. Howells, T. Ognibene, M. Malfatti, C. Goldring, N. Kitteringham, J. Walsh, M. Viskaduraki, K. West, A. Miller, D. Hemingway, W. P. Steward, A. J. Gescher, K. Brown, Cancer chemoprevention: Evidence of a nonlinear dose response for the protective effects of resveratrol in humans and mice. Sci. Transl. Med. 7, 298ra117 (2015). [Abstract]