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The chemical resveratrol found in grape skins and in red wine may prevent cancer. With hard alcohol that’s the end of the story: increased risk for head and neck cancer due to increased production of acetyl aldehyde
A natural substance present in red wine, resveratrol, inhibits the formation of inflammatory factors that trigger cardiovascular diseases. This has been established by a research team at the Department of Pharmacology of the University Medical Center of Johannes Gutenberg University of Mainz (JGU) working in collaboration with researchers of the Friedrich Schiller University in Jena and the University of Vienna. Their results have recently been published in the scientific journal Nucleic Acids Research.
Despite the fact that they eat more fatty foods, the French tend to less frequently develop cardiac diseases than Germans. This so-called French Paradox is attributed to the higher consumption of red wine in France and it has already been the subject of various studies in the past. A number of research projects have actually demonstrated that the natural product resveratrol, present in red wine, has a protective effect against cardiovascular diseases. But what exactly is the reason for this? It seems that at least part of the protective effect can be explained by the fact that resveratrol inhibits the formation of inflammatory factors, a conclusion reached by the research team of Junior Professor Andrea Pautz and Professor Hartmut Kleinert of the Mainz University Medical Center following collaboration in a joint project with Professor Oliver Werz of the Friedrich Schiller University in Jena and Professor Verena Dirsch of the University of Vienna. In fact, the researchers discovered that the natural substance binds to the regulator protein KSRP and activates it. KSRP reduces the stability of messenger RNA (mRNA) in connection with a number of inflammatory mediators and thus inhibits their synthesis.
"We now know more precisely how resveratrol inhibits the formation of the inflammatory factors that trigger cardiovascular diseases. This is an important finding in view of the fact that more recent research has shown that cardiovascular diseases are significantly promoted by inflammatory processes in the body," said Pautz. Cardiovascular disorders, such as myocardial infarction and strokes, frequently occur in association with chronic inflammatory diseases, such as arthritis. The natural substance resveratrol thus has major therapeutic potential, particularly when it comes to the treatment of inflammatory diseases that can cause serious damage to the cardiovascular system.
Alcohol use is a major risk factor for head and neck cancer. But an article published in the November issue of the journal Advances in Experimental Medicine and Biology shows that the chemical resveratrol found in grape skins and in red wine may prevent cancer as well.
“Alcohol bombards your genes. Your body has ways to repair this damage, but with enough alcohol eventually some damage isn’t fixed. That’s why excessive alcohol use is a factor in head and neck cancer. Now, resveratrol challenges these cells – the ones with unrepaired DNA damage are killed, so they can’t go on to cause cancer. Alcohol damages cells and resveratrol kills damaged cells,” says Robert Sclafani, PhD, investigator at the University of Colorado Cancer Center and professor of biochemistry and molecular genetics at the CU School of Medicine.
Some of what we know about the ability of alcohol to cause cancer comes from the study of another disease, namely Fanconi anemia, a rare genetic disorder that affects about 1 in every 350,000 babies. DNA naturally accumulates tangles called “cross links” and healthy genes can repair and disentangle cross-linked DNA. In Fanconi anemia, people are born without the ability to repair DNA cross links and so DNA damage accumulates. Accordingly, patients with Fanconi anemia are at greatly increased risk of developing cancers including leukemias and also head and neck cancer.
“We learn a lot from genetic disorders because you can put a finger on a gene and say, hey, we know what that does!” says Sclafani, who has presented at and regularly attends the annual meeting of the Fanconi Anemia Research Foundation.
In fact, it turns out that a genetic accelerator of cancer in Fanconi anemia is the same as the cancer-causing mechanism of alcohol. In both cases, the cause is partially metabolized alcohol. The body metabolizes alcohol by converting it first to acetyl aldehyde and then the body uses aldehyde dehydrogenase (ALDH) to further convert it to acetic acid, which is excreted. The partially processed state of alcohol, acetyl aldehyde, is a carcinogen and produces “cross links” in DNA.
Because Fanconi anemia patients cannot repair the DNA damage produced by acetyl aldehyde, they are at even higher risk for cancer if they also lack ALDH.
“With enough alcohol, the body can get behind and end up with a backlog of acetyl aldehyde,” Sclafani says. “Increased exposure to alcohol, loss of the ALDH gene that helps the body process alcohol, and loss of the ability to repair DNA cross links all result in increased cancer risk.”
With hard alcohol that’s the end of the story: increased risk for head and neck cancer due to increased production of acetyl aldehyde.
“But when you look at epidemiological studies of head and neck cancer, alcohol is a factor, but by alcohol source, the lowest cancer incidence is in people who drank red wine,” Sclafani says. “In red wine, there’s something that’s blocking the cancer-causing effect of alcohol.”
The recent article points to resveratrol as Sclafani’s “something”.
Sclafani describes the effects of resveratrol in terms of probability: “The more you drink, the more you accumulate DNA damage, and the more chance that one or more cells will accumulate the specific type of DNA damage that can cause cancer. Now, resveratrol takes out the cells with the most damage – the cells that have the highest probability of being able to cause cancer.”
According to Sclafani, the resveratrol in red wine (and other chemopreventive chemicals found in grape seed extract) isn’t a magic bullet that can completely undo the cancer-causing effects of alcohol, but by killing the most dangerous cells it may decrease the probability that alcohol use will cause cancer.
“Because alcohol-related head and neck cancer has a high rate of recurrence, after a cancer has been treated once, you’ve still got a very high-risk population,” Sclafani says.
by R. T.
14 december 2014, Technical Area > Grapevine & Wine