Metformin, pictured here in molecular form, is one of the world's most commonly prescribed antidiabetic drugs. It appears to interfere with the production of reactive oxygen species (ROS) in mitochondria. The mechanism could explain the observation, first made in 2005, of reduced cancer rates among metformin users.
By Tyler Irving
Posted March 2012
Metformin is one of the world’s most widely prescribed antidiabetic drugs. Now, Canadian research has shed light on how it may also act to combat cancer.
In 2005, an epidemiological study by researchers at the University of Dundee showed that diabetics being treated with metformin had significantly lower cancer rates than those on other treatments. This intrigued McGill University oncologist Michael Pollack, who in turn contacted biochemist Gerardo Ferbeyre at Université de Montréal. Ferbeyre and his colleagues research how human cells defend themselves against genetic mutations that can cause cancer. One common cause of these mutations is reactive oxygen species (ROS) produced by mitochondria as a byproduct of metabolism. These reactive chemicals can damage DNA.
In vitro studies showed that unlike antioxidants, which prevent cancer by reacting with ROS before they can damage DNA, metformin appears to prevent mitochondria from forming ROS in the first place. “I use the analogy of a leaky faucet,” says Ferbeyre. “Using an antioxidant is like trying to clean up the water with a towel. Metformin would be like turning off the tap.” This was further demonstrated with an in vivo experiment using the pesticide paraquat, which causes overproduction of ROS. Mice treated with paraquat and metformin survived significantly longer than those treated with paraquat only.
Despite these promising results, Ferbeyre cautions that more research is needed. “Even if the drug has been used for many years, we need the pilot studies on populations at risk before recommending it to the general public.” He adds that one such trial: using metformin to increase the efficiency of chemotherapy, will be starting at the University of Toronto. Ferbeyre and Pollack’s results are published in Cancer Prevention Research.
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