Researchers studying the actions of trans-resveratrol (Res), a natural substance found in red wine, are one step closer to discovering the molecular basis for its chemopreventive and anti-inflammatory effects. The new data may explain how red wine protects against cardiovascular disease and certain cancers - the so-called "French Paradox".

Minnie Holmes-McNary and Albert Baldwin (University of North Carolina, NC, USA) used human and rat cell lines to determine the actions of Res - known to mediate cancer chemopreventive activity in animals - on transcription factor NF-kB. NF -kB is required by tumour cells for proliferation and , once activated by a key regulatory complex IKK, NF -kB is able to translocate into the nucleus of cells and activate gene expression. Activated NF -kB has been found in primary breast tumours and works, in part, by preventing normal apoptosis (programmed cell death) of potentially cancerous cells.

"We showed that Res was a potent inhibitor of both NF -kB activation and NF -kB dependent gene expression", reports Holmes McNary (Cancer Res 2000; 60: 3477-83). Furthermore, Res induced apoptosis of potentially cancerous cells.

"Our results suggest that the major mechanism whereby Res blocks NF -kB activity is through the inhibition of IKK activity." This finding may partly explain how Res could inhibit onco-genic and inflammatory disease in human beings.

John Pezzuto (Universty of Illinois, Chicago, IL USA) explains that there is currently much interest in Resveratrol as it can be obtained from the diet. "While its likely that alteration of NF-kB is not only a mechanism facilitated by Res", he states, "these findings represent an important piece of the overall puzzle". The National Cancer Institute has recently initiated preclinical toxicity studies on Resveratrol that should lead to clinical trials.