August 15, 2007
Metformin slows growth of tumors lacking p53
The July, 2007 issue of
Cancer Research published the results of research conducted at the University of Pennsylvania School of Medicine which determined that metformin, a drug commonly used for
diabetes, destroys tumor cells lacking a regulatory gene known as p53, which acts as a tumor suppressor. The gene is estimated to be lost in over half of all human cancers.
Studies have found that diabetics who use metformin have a lower risk of cancer and mortality within a given period than those who don't use the drug. In research funded by the National Cancer Institute, University of Pennsylvania Professor of Cancer Biology and Medicine Craig B. Thompson MD and colleagues injected human colon cancer cells with normal p53 into one side of mice and the same cells lacking p53 into the other side. After four days, the mice received daily injections of metformin or saline. The dose of metformin administered in the study was equivalent to that used by human diabetics.
At the end of the four week treatment period there was no difference among the animals in the size of tumors with normal p53, however, tumors lacking p53 in mice that received metformin were half the size of those in the saline-injected animals. The team discovered that the drug instructs cells to switch metabolic pathways from oxidative phosphorylation, the most energy efficient pathway, to a stress related one used when the cells are deficient in oxygen, glucose or other nutrients. Normally when p53 is absent, the cells are not able to perform the switch. “Without p53, if we force cells to live on alternative substrates, they can’t do it,” explained Dr Thompson .
He announced, “This is the first time you can show that tumor growth is impaired by a diabetes drug. It is specific for tumors that lack p53, which is the most common mutation in human cancer.”
—D Dye