In 2005, news broke that researchers in Scotland found low rates of cancer among diabetics taking metformin, a drug commonly prescribed to patients with Type 2 diabetes. Many follow-up studies reported similar findings, some suggesting as much as a 50% reduction in risk.

How could the antidiabetic drug reduce the risk of developing cancer and what were the mechanisms involved?

Researchers from McGill University and the University of Montreal reported an unexpected finding: Exposure to metformin reduces the cellular mutation rate and the accumulation of DNA damage. It is known that such mutations are directly involved in carcinogenesis, but lowering cancer risk by inhibiting the mutation rate has never been shown to be feasible.

"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,” explains Michael Pollak, MD, professor in McGill's Medicine and Oncology Departments.

The study suggests that metformin reduces DNA damage by reducing levels of reactive oxygen species (ROS). ROS are known to be DNA-damaging agents produced as byproducts when cells generate energy from nutrients. The action appears to take place in the mitochondria. While past studies have identified the mitochondria as a site of action for metformin related to its anti-diabetic function, the studies had not considered that the drug also acted to reduce ROS production. "We found that metformin did not act as a classic antioxidant," says Gerardo Ferbeyre, MD, University of Montreal's Department of Biochemistry. "The drug seems to selectively prevent ROS production from altered mitochondria such as those found in cells with oncogenic mutations."

"This doesn't imply 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,” says Pollak. “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."

The research was published in Cancer Prevention Research.

Release Date: Jan. 18, 2012
Source: McGill University