Geneticists Find Clue to Red-Wine Compound's Role as Possible Cancer Fighter
Resveratrol may act by turning off genes that cause prostate cells to become cancerous
Recent medical research points to resveratrol as a promising compound in preventing the growth of cancer cells. Now geneticists at Stanford University in California report that they may have figured out how the red-wine polyphenol fights cancer on a genetic level.
By exposing cancerous prostate cells to resveratrol in the lab and examining their DNA, the scientists say they may have witnessed the compound working its anticancer magic. But, they say, making resveratrol an effective treatment for humans is still a long way off.
Study coauthor James Brooks said that resveratrol's influence on gene behavior within cancer cells is complicated, but that the compound appeared to influence the way the cells handle male hormones called androgens.
Androgens, including testosterone, are major suspects in the pathology of prostate cancer, which killed an estimated 29,900 Americans last year, according to the study. In the research, resveratrol seemed to block the cancer cells from "communicating" with the androgen, thereby preventing the cells from growing and reproducing. The findings appeared in the March issue of Cancer Epidemiological Biomarkers and Prevention.
The researchers don't know if drinking red wine would have a similar effect, but last year, a study from the Fred Hutchinson Cancer Research Center in Seattle found that people who drink wine in moderation appeared to have half the risk of developing prostate cancer as nondrinkers and beer and liquor drinkers. The authors of that study believe the differences may be attributable to the polyphenols in red wine, including resveratrol, which is abundant in grapes (particularly the skins) and some other foods.
Resveratrol has shown other potential health benefits in research. Numerous studies have linked moderate consumption of alcohol, in particular red wine, to improved cardiovascular health, and some research indicates that resveratrol may contribute to that by reducing cholesterol levels. Other recent studies have found that resveratrol may help alleviate some lung diseases, reduce the growth of skin melanomas and damage caused by sunburn and extend the longevity of some basic organisms.
When it comes to fighting cancer, the mechanism by which resveratrol may work is still not clear. One study published in 2000 found that the compound deactivates a particular protein gene that protects cancer cells from chemical treatments. A 2002 study reported that when resveratrol reaches a tumor, an enzyme converts it into another chemical that is toxic to cancer cells.
Brooks believes his team's results show that resveratrol may work in multiple ways to fight cancer. For example, in addition to its observed effect on androgen, it may help regulate enzymes used in carcinogen defense systems.
For their lab experiments, Brooks and his team used manufactured resveratrol and cultured cancer cells with androgen. The scientists left one group of cancer cells alone to incubate as a control and exposed the other cells to solutions of 25, 75 or 150 micromoles of resveratrol per liter. Then they checked the samples every three hours for several days.
The higher the dose and the longer the exposure, the more effective resveratrol seemed to be. After 60 hours, for example, the researchers found that the 25 micromolar solution slowed cell growth and proliferation by 16 percent compared with the control group. In contrast, the 75 micromolar sample slowed reproduction by 83 percent and the 150 micromolar sample by 86 percent. The tests were repeated with similar results.
The team examined the samples using DNA microarray analysis, a technique that allowed them to check which genes in the cells were turned "on" or "off" and to make comparisons between resveratrol-treated cancer cells and untreated cells, Brooks explained. "The advantage of this method is that it can uncover pathways and genes that we never suspected were affected by resveratrol," he said.
Among the tens of thousands of genetic pathways, they found that the cells treated with resveratrol seemed to block androgen from turning on the cancerous prostate cells and causing proliferation. "Understanding how resveratrol blocks androgen signaling and cell growth could lead to therapies that target these pathways," Brooks said.
Much more work is needed, Brooks noted. The DNA data is so voluminous that his team has yet to examine all of it, so they have posted it online for other geneticists to mull over. "I am sure we have uncovered only a few of the things that resveratrol does," Brooks said, "and we hope that others will use it to make additional findings that help us understand how resveratrol works in prostate cells."
