19-1-97 Guardian Weekly Anti-cancer agent found in grapes - Tim Radford

GRAPES and wine contain a natural antidote to cancer, scientists reported last week, a discovery that could help explain the so-called "French paradox" - the lower rates of heart disease and cancer of nations such as France, Italy and Spain. John Pezzuto of the Illinois College of Pharmacy in Chicago and other scientists reported in the US journal Science that they tested a plant substance called resveratrol and found it showed cancer-preventative activity in three major stages of tumour formation.'they found high quantities of resveratrol in grapes and fresh grape skin, and up to three milligrams per litre in red wine. "Appreciable amounts are also found in white and rose wines," they report. Resveratrol acted as an anti-oxidant and antimutagen, blocking other cell-changing agents from starting cancer. It also acted in a number of ways to stop the promotion of cancer, and inhibited the progress of human leukaemia-cell forniation. Cancer is the largest cause of death worldwide, taking one life in five. 'Resveratrol merits investigation as a potential cancer chemo-preventive agent," the scientists conclude. Nobody knows for certain what resveratrol does in plants.

It has been found in at least 72 species including mulberries, peanuts and grapes. It is thought to be one of a class caged phytoalexins, produced by plants when they are stressed by fungal attack. Wine - and red wine in particular - was already known to offer some kind of protection against heart disease. This may be because it prevents the build- up of platelets in the blood. The latest discovery supports what herbalists and botanists say. Many plants contain useful and as yet unidentified agents for the treatment and prevention of disease - including cardio-vascular diseases and cancer. And it reinforces the new interest in low-fat and high-fibre diets as a way of reducing cancer risk. The US National Cancer Institute believes that diet is responsible for 35 per cent of all cancers. But Dr Pegzuto is not, for the time being, recommending chemotherapy by the claret glass or a prophylactic pinot noir. Alcohol is dangerous in other ways. Grapes and grape juices would be a healthier choice. 'We are a bit concerned," said Dr Pezzato. 'Obviously this is related to the so-called French paradox, with wine consumption being inversely related to heart problems. 'The good news is that we have things in wine and grape products that can possibly prevent cancer. The other side of the coin is that there tends to be a positive correlation between cancer and alcohol - with breast cancer, for example. So at best what we have here is some kind of neutralising effect."

Chateau Estrogen New Scientist Jan 3 98

WINE contains a chemical that acts just like the hormone oestrogen. The chemical might explain why moderate drinking appears to help prevent heart disease. Scientists have long been trying to explain the so-called "French paradox". The French have a diet that is fairly high in fat, yet they suffer little heart disease. Wine, for which the French have a passion, may play a role. Previous studies showed that grape skins contain a natural compound called resveratrol. This may help the heart by keeping fragments of cells called platelets from forming dangerous blood clots, and also by reducing inflammation. Now Barry Gehm of Northwestern University Medical School in Chicago, Illinois, has come up with an alternative idea. He happened to glance at a diagram of resveratrol's chemical structure, and immediately realised that it looked very much like diethylstilbestrol, a synthetic oestrogen. Several laboratory tests confirmed Gehm's suspicion that resveratrot acts like a hormone. For instance, his team added resveratrol and radioactively labelled oestrogen to cell lines with oestrogen receptors. They found that when they increased concentrations of resveratrol, the amount of oestrogen binding to the receptors decreased. This indicated that the two compounds were competing for space on oestrogen receptors.

Not only did resveratrol bind to oestrogen receptors, it also activated them. The researchers learnt this by using cells that were genetically engineered to express luciferase-the protein that can make fireflies glow whenever the target genes of the oestrogen receptors were switched on (Proceedings of the National Academy of Sciences, vol 94, p 14 138). Because oestrogen affects cholesterol levels and the lining of blood vessels, Gehm believes this finding eart attacks could provide an alternative explanation for why red wine helps to prevent heart disease. But he stresses that no one knows what resveratrol from wine actually does in the body. "It's going to be a close call as to whether people ingest enough of resveratrol for it to have any oestrogenic effects," says Gehm. Nell Boyce