Heart Drugs May Play Anticancer Role

Cancer researchers have found that a group of drugs currently used to treat irregular heart rhythms and heart failure block the growth of prostate tumors and have considerable potential for development into anticancer therapeutic agents.

Investigators at Johns Hopkins University (Baltimore, MD, USA) screened a library of more than 3,000 drugs that are already FDA approved or currently being tested in phase II clinical trials for their ability to inhibit hypoxia-inducible factor (HIF-1), a protein that controls genes that enable cells to stay alive under low-oxygen conditions. HIF-1 activates genes that stimulate the growth of new blood vessels that allow oxygen-starved cells to survive in regions of low oxygen concentration such as are found within fast-growing solid tumors.

Results published in the November 19, 2008, online edition of the Proceedings of the [U.S.] National Academy of Sciences (PNAS) revealed that 20 drugs inhibited HIF-1-dependent gene transcription by more than 88%. Eleven of these drugs were cardiac glycosides, including digoxin, ouabain, and proscillaridin A, which inhibited HIF-1-alpha protein synthesis and expression of HIF-1 target genes in cancer cells.

The investigators then focused on digoxin because of its already well-established clinical utilization. They found that digoxin treatment of prostate cancer cells grown at normal and low-oxygen levels resulted in significant slowing of cell growth, with fewer total cells, and increased numbers of cells that ceased growing. Digoxin treatment suppressed growth of human prostate tumors that had been transplanted into mice. HIF-1 levels were lower in tumors from treated animals than those taken from untreated control mice.

"Oxygen-deprived cancer cells increase their HIF-1 levels to survive in these unfavorable conditions,” explained senior author Dr. Gregg L. Semenza, professor of genetic medicine at Johns Hopkins University. "So turning down or blocking HIF-1 may be key to slowing or stopping these cells from growing. 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.”


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