1930s drug slows tumor growth

Drugs sometimes have beneficial side effects. A glaucoma treatment causes luscious eyelashes. A blood pressure drug also aids those with a rare genetic disease. The newest surprise discovered by researchers at the Johns Hopkins University School of Medicine is a gonorrhea medication that might help battle cancer.

"Often times we are surprised that a drug known to do something else has another hidden property," says Jun Liu, Ph.D., a professor of pharmacology and molecular sciences at Johns Hopkins and author on the study published Oct. 1 in the Proceedings of the National Academy of Sciences.

In this case, the surprise is a big one. The drug, acriflavine, used in the 1930s for treating gonorrhea, has turned out to have the previously unknown ability to halt the growth of new blood vessels. Preliminary tests showed that mice engineered to develop cancer had no tumor growth if treated with daily injections of acriflavine.

"As cancer cells rapidly divide, they consume considerable amounts of oxygen," says Gregg Semenza, M.D., Ph.D., the C. Michael Armstrong Professor of Pediatrics and director of the vascular program at the Johns Hopkins Institute for Cell Engineering. "To continue growing, a tumor must create new blood vessels to deliver oxygen to the tumor cells."

Acriflavine stops blood vessel growth by inhibiting the function of the protein hypoxia-inducible factor (HIF)-1, which was discovered by Semenza's team in 1992. When HIF-1 senses that the surrounding environment is low in oxygen, it turns on genes necessary for building new vessels. Though essential for normal tissue growth and wound healing, HIF-1 is also turned on by cancers to obtain the oxygen they need to survive. Most importantly, in order for HIF-1 to work, two subunits must bind together like puzzle pieces.