Digitalis-based drugs like digoxin have been used for centuries to treat patients with irregular heart rhythms and heart failure and are still in use today.
In the Dec. 16 issue of the Proceedings of the National Academy of Sciences, researchers at the Johns Hopkins University School of Medicine now report that this same class of drugs may hold new promise as a treatment for cancer. This finding emerged through a search for existing drugs that might slow or stop cancer progression.
"This is really exciting, to find that a drug already deemed safe by the FDA also can inhibit a protein crucial for cancer cell survival," says Gregg L. Semenza, M.D., Ph.D., director of the vascular program at the Johns Hopkins Institute for Cell Engineering and a member of the McKusick-Nathans Institute of Genetic Medicine.
Semenza and his team have long studied the hypoxia-inducible factor, or HIF-1, protein, which controls genes that help cells survive under low-oxygen conditions. HIF-1 turns on genes that grow new blood vessels to help oxygen-starved cells survive. Regions of low oxygen are common within the environment of fast-growing solid tumors.
"Oxygen-deprived cancer cells increase their HIF-1 levels to survive in these unfavorable conditions," says Semenza. "So turning down or blocking HIF-1 may be key to slowing or stopping these cells from growing."
The researchers took advantage of the Johns Hopkins Drug Library, a collection of more than 3,000 drugs already FDA approved or currently being tested in phase II clinical trials, assembled by Hopkins pharmacology professor Jun O. Liu. In this study, the research team tested every drug in the library for its ability to turn down HIF-1in cancer cells. The top 20 candidates identified were able to reduce HIF-1 by more than 88 percent, and more than half of these 20 belong to a class of drugs already commonly used for treating heart failure, and included digoxin.
The researchers focused on digoxin because of its already well-established clinical use. They treated prostate cancer cells grown at normal and low-oxygen levels with digoxin for three days and counted the number of cells each day. They found that cells treated with digoxin significantly slowed their growth, with fewer total cells after three days and increased numbers of cells that had stopped growing when compared to untreated cells.