By Laura Crowley 27-Mar-2008 – The antioxidant resveratrol, found in grape skins and red wine, can cripple the function of pancreatic cancer cells while sensitising them to chemotherapy, says new research. Resveratrol is known for its ability to protect plants from bacteria and fungi, while previous research has also found it helps prevent the negative effects of high-calorie diets and has anti-inflammatory and anti-cancer potential. While this study, published this month in Advances in Experimental Medicine and Biology, looked at the way the antioxidant may aid pancreatic cancer treatment, it also contributes to the growing knowledge on the health benefits arising from ingredients of red wine. As well as disabling the function of the cancer cells by reaching and reacting with the mitochondria (the cell's energy source), researchers found that when they were pre-treated with resveratrol before being irradiated, it resulted in a type of cell death called apoptosis. This is an important goal of cancer therapy. "Antioxidant research is very active and very seductive right now," said Paul Okunieff, chief of radiation oncology at the University of Rochester Medical Centre. "The challenge lies in finding the right concentration and how it works inside the cell. Resveratrol seems to have a therapeutic gain by making tumour cells more sensitive to radiation and making normal tissue less sensitive." The study To build on such findings, Okunieff began studying resveratrol as a tumour sensitizer, which is when the link to the mitochondria was uncovered. Researchers divided pancreatic cancer cells into two groups: cells treated without resveratrol then iodised, and ones treated with resveratrol at a relatively high dose of 50mg per ml before being iodised. The amount of resveratrol in red wine can vary between types of grapes and growing seasons, and ranges can be as high as 30 mg per ml. But the researchers said higher doses are expected to be safe as long as a physician monitors the patient. The study found that resveratrol reduced the function of proteins in the pancreatic cancer cell membranes responsible for pumping chemotherapy out of the cell, therefore making them more sensitive to the treatment. Additionally, the antioxidant triggered the production of reactive oxygen species (ROS), causing apoptosis, and depolarised the mitochondrial membranes, indicating a decrease in the cell's potential to function. The researchers said the discovery is important because the mitochnodria contains its own DNA and can continuously supply the cell with energy when functioning fully. Stopping the energy flow can therefore help stop cancer. In investigating why the pancreatic cancer cells are particularly resistant to chemotherapy and therefore reactive to the inclusion of resveratrol, the team found that the natural pumping of digestive enzymes to the duodenum actually flushes out chemotherapy from pancreas cells. But as resveratrol interferes with the cancer cells' energy source, it also may decrease the power available to pump the treatment out of the cell. Okunieff said: "While additional studies are needed, this research indicated that resveratrol has a promising future as part of the treatment for cancer." Sources Advances in Experimental Medicine and Biology 2008;614:179-86 "Anti-cancer effect of resveratrol is associated with induction of apoptosis via a mitochondrial pathway alignment" Authors: Paul Okunieff, Weimin Sun, Wei Wang, Jung Kim, Shanmin Yang