Exciting new research has found that men who take digoxin, a drug used to treat congestive heart failure and arrhythmia, may have a lower risk of being diagnosed with prostate cancer. The work was led by Elizabeth A. Platz, Sc.D., M.P.H., the Beth W. and A. Ross Meyers Scholar, and colleagues at Hopkins and Harvard, and was built on other recent Hopkins findings.(Related work on the use of statin drugs was covered in the article "Statins: Drugs that Lower Cholesterol May Help Ward off Lethal Prostate Cancer" in Discovery 2009). First, scientists Jun Liu, Ph.D., Srinivasan Yegnasubramanian, M.D., Ph.D., and William G. Nelson, M.D., Ph.D., tested many currently available drugs — already being used to treat other health problems — on prostate cancer cells. (The great advantage to finding new uses for current drugs is that they have already been through the rigorous and time-consuming testing required by the Food and Drug Administration and similar agencies.) Their laboratory work showed that digoxin halted the growth of the prostate cancer cells. In a second study, Liu and Gregg L. Semenza, M.D., Ph.D., found some clues as to how it may work: It turns out that digoxin decreases the amount of a protein called HIF-1. "This protein signals other cells to make new blood vessels, which bring additional oxygen and nourishment to a cancer and allow it to grow even more," explains Platz.
Men taking digoxin have a lower
risk of getting prostate cancer.
The next step was to see if digoxin protects against prostate cancer in men who take it to treat their heart problems. Platz and the Hopkins team collaborated with investigators at Harvard in charge of the Health Professionals Follow-Up Study, a group of 47,759 men who have been followed since 1986. In that study, the men, who are between 40 and 75 years old, and free of a cancer diagnosis when they first start participating, are asked every two years about the medications they take. At the start of the study, 2 percent of men said that they regularly used digoxin. By 2006, 5,008 of the men had been diagnosed with prostate cancer.
"We found that men who regularly used digoxin at the start of the study had about a 25-percent lower risk of getting prostate cancer than men who were not using the drug," says Platz. "This was true whether they used the drug to treat congestive heart failure or arrhythmia." Because men who have many health problems may be less likely to be screened for prostate cancer, the team also looked among men who had taken a PSA test. Again, they found that men on digoxin had a lower risk of prostate cancer. "There was even evidence that men who took digoxin for 10 or more years had the lowest risk of prostate cancer," Platz adds. "Their risk was 40 percent lower than that of men who had never used digoxin."
Platz and colleagues anticipate that the results of the Hopkins studies on digoxin, when taken together, will help scientists looking for drugs to treat prostate cancer and to prevent this cancer from developing. "The digoxin work gives us new prostatespecific pathways to explore," she says. Already, medical oncologists at Hopkins are planning a clinical trial to test the use of digoxin in men who already have prostate cancer. "This work demonstrates how when investigators from many different disciplines work together, discoveries that hold the promise of prostate cancer prevention and treatment may be made more efficiently."
An anti-inflammatory agent may help prevent prostate cancer from returning: In other collaborative work, Platz and colleagues Alan Meeker, Jay Bream, Charles Drake, George Netto, Angelo De Marzo, and William Isaacs, are investigating whether a naturally produced anti-inflammatory agent, known as interleukin-10 (IL-10), can ward off prostate cancer. In previous work, they found that men who carried a particular version of the gene that makes IL-10 were less likely to develop prostate cancer — and also less likely to have the cancer come back after radical prostatectomy. "Cytokines are chemicals released by white blood cells," notes Platz. "This particular cytokine, IL-10, by keeping down inflammation, may indirectly keep prostate cancer from becoming more aggressive." Platz and her colleagues currently investigating this have expertise in epidemiology, pathology, immunology, molecular biology, and urology.
Bottom Line: Digoxin Helps Prevent Prostate Cancer
Men who regularly used digoxin at the start of the study had about a 25-percent lower risk of prostate cancer than other men. Men who took digoxin for 10 or more years had the lowest risk of prostate cancer; their risk was 40 percent lower than that of men who had never used digoxin. These results give scientists new, prostate-specific pathways to explore in looking for new drugs to treat prostate cancer.