Metformin Lowers Cancer Risk by Preventing Formation of Reactive Oxygen Species

The drug metformin, which is used to treat type II diabetes, has been found to reduce cancer risk by blocking the formation of reactive oxygen species (ROS) that cause the type of DNA damage that leads to tumor development.

Metformin is used alone or with other medications, including insulin, to treat type II diabetes. The drug helps to control the amount of glucose in the blood by decreasing the amount of glucose absorbed from food and the amount of glucose made by the liver. Metformin also increases the body's response to insulin. Metformin is not used to treat type I diabetes where the body does not produce insulin due to autoantibodies that attack pancreatic beta cells.

Investigators at McGill University (Montreal, Canada) and the University of Montreal (Canada) reported in the January 18, 2012, online edition of the journal Cancer Prevention Research that they had found that metformin attenuated elevations in ROS and related DNA damage and mutations induced by exposure to the toxic herbicide paraquat. However, the drug had no effect on similar changes induced by hydrogen peroxide, indicating a reduction in endogenous ROS production. Importantly, metformin also inhibited Ras-induced ROS production and DNA damage.

“It is remarkable that metformin, an inexpensive, off-patent, safe and widely used drug, has several biological actions that may result in reduced cancer risk – these latest findings suggest that it reduces mutation rate in somatic cells, providing an additional mechanism by which it could prevent cancer,” said senior author Dr. Michael Pollak, professor of medicine and oncology at McGill University.

“This study opens an exciting new direction in cancer-prevention research,” said Dr. Pollak. “This does not imply, however, that metformin is now ready to be widely used for cancer prevention. We do not yet know if the drug accumulates to sufficient concentrations in human tissues at risk for cancer, such as breast or colon, when taken at the usual doses used for diabetes treatment, nor do we know if the findings from the original studies showing reduced cancer risk, which were carried out in diabetics, also apply to people without diabetes. But the possibility of protecting DNA from oxidative damage by the use of a well-tolerated drug was not expected, and this topic now needs further study at many levels.”

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