A team of researchers from the University of Leicester’s Department of Cancer Studies and Molecular Medicine have demonstrated that a chemical found in red wine remains effective at fighting cancer even after the body’s metabolism has converted it into other compounds.
The results of this study , published in the journal Science Translational Medicine, reveals resveratrol — a compound extracted from the skins of red grapes – is not rendered ineffective once it is metabolized by the body.
Resveratrol is metabolized very quickly in the body, and scientists had previously thought levels of the extracted chemical drop too quickly to make it usable in clinical trials. The new research, however, reveals resveratrol can still be absorbed into cells after it has been metabolized into resveratrol sulfates.
Cell enzymes break the sulfates down into resveratrol again, making the levels of the chemical in cells higher than previously thought. The study findings suggest the resveratrol generated from metabolized sulfates may be more effective than pre-metabolized resveratrol because the concentrations are higher.
Professor Karen Brown, translational cancer research expert at the University of Leicester, led the team of researchers that administered resveratrol sulfate to mice models. The researchers were subsequently able to detect free resveratrol in plasma and a variety of tissues in the mice — the first direct sign that resveratrol can be formed from resveratrol sulfate in live animals. The research team hopes that this sign will help to show how resveratrol is able to have beneficial effects in animals.
The results also revealed resveratrol generated from resveratrol sulfate is able to slow the growth of cancer cells. The generated resveratrol does this by causing cancer cells to digest their own internal constituents and stopping them from dividing.
Professor Brown said, “There is a lot of strong evidence from laboratory models that resveratrol can do a whole host of beneficial things – from protecting against a variety of cancers and heart disease to extending lifespan.
“It has been known for many years that resveratrol is rapidly converted to sulfate and glucuronide metabolites in humans and animals – meaning the plasma concentrations of resveratrol itself quickly become very low after administration,” she said.
“It has always been difficult to understand how resveratrol is able to have activity in animal models when the concentrations present are so low, and it has made some people skeptical about whether it might have any effects in humans,” said Brown.
She noted scientists have hypothesized for a long time that resveratrol might be regenerated from its major metabolites in whole animals. Until now, however, it has never been proven.
“Our study was the first to show that resveratrol can be regenerated from sulfate metabolites in cells and that this resveratrol can then have biological activity that could be useful in a wide variety of diseases in humans,” Brown added.
“Importantly, we did all our work with clinically achievable concentrations so we are hopeful that our findings will translate to humans. Overall, I think our findings are very encouraging for all types of medical research on resveratrol. They help to justify future clinical trials where, previously, it may have been difficult to argue that resveratrol can be useful in humans because of the low detectable concentrations,” said Brown.
“There is considerable commercial interest in developing new forms of resveratrol that can resist or overcome the issue of rapid metabolism. Our results suggest such products may not actually be necessary to deliver biologically active doses of resveratrol to people.”
The eight-year study was supported by the Cancer Research UK and National Institute for Health Research (NIHR) Experimental Cancer Medicine Centre in Leicester, and the US National Cancer Institute.
Dr Sarah Williams, Cancer Research UK health information officer, said, “This interesting study supports continued research into resveratrol as a therapeutic molecule, but it’s important to note that any benefits from the molecule don’t come from drinking red wine. It’s well established that drinking any type of alcohol, including red wine, increases the risk of developing cancer.”
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