Rajesh Agarwal, PhD, investigator at the University of Colorado Cancer Center

Resveratrol, a chemical found in red wine and peanuts, exploits a genetic difference between healthy and cancerous cells in head and neck tumors to selectively kill the cancerous cells while leaving healthy cells unharmed.

“This is a major breakthrough kind of thing,” says Rajesh Agarwal, PhD, investigator at the University of Colorado Cancer Center and professor of pharmaceutical sciences at the University of Colorado School of Pharmacy, who partnered on the study with Robert Sclafani, also of the Cancer Center and professor of biochemistry and molecular genetics at the School of Medicine.

The way it works is this: in both healthy and cancerous cells, cell division takes place in three phases. During the middle phase – S-phase – the cell makes a copy of its DNA that will then build the new cell. As you might guess, accurate replication of this DNA is, as Martha Stewart would say, a good thing – healthy cells have extensive repair machinery to ensure that any mutations during this S-phase are quickly and accurately repaired; lack of ability to repair DNA damage can allow a cell to mutate into something new, sometimes something cancerous.

Resveratrol intercedes in S-phase to damage newly-replicated cell DNA. “The healthy cells can repair the damage, but cancer cells can’t and when we treat cancer cells with resveratrol, we see arrest in the S-phase,” says Agarwal. In healthy cells, the repair is instant and makes no difference to the newly-born copy whatsoever, but the lack of repair that allows a cell to become cancerous also makes it fragile – to most cells implicated in head and neck squamous cell carcinomas, the DNA damage of resveratrol during S-phase is fatal. The damaged DNA can’t successfully build the new cell and the spread of cancer is stopped cold.

It’s a nifty trick that exploits a fundamental biological difference between healthy and cancerous cells to kill cancer but not tissue we’d rather keep.

“The population we’d like to focus on is patients who’ve already undergone treatment for head and neck cancers – who are at high risk for recurrence at a rate of about 50%,” says Robert Sclafani. Specifically, cancers of the oral cavity are a likely first target for resveratrol-based treatments, due to the ease of drug delivery via oral mouthwash.

Until then: “We had one cell line that was so sensitive to resveratrol that a glass of red wine would probably have worked,” says Sclafani.

Robert Sclafani, PhD, investigator at the Colorado Cancer Center

But, “You can’t just drink more wine,” says Agarwal, who points out that consuming the level of resveratrol needed to kill the vast majority of head and neck cancers through red wine is simply impractical. But, while more research is needed, Agarwal muses that perhaps a glass of wine per night combined with the resveratrol found in peanut-rich Thai food could be a moderate prophylactic against the development of head and neck cancers.

Published OnlineFirst June 24, 2011; doi: 10.1158/1078-0432.CCR-11-1072

Funding provided by CCTSI (Colorado Clinical and Translational Sciences Institute

NIH/NCRR #UL1-RR025780) co-pilot grant and University of Colorado Cancer Center Aging and Cancer Seed grants (NIH/NCI P20CA103680)

awarded to RAS.