Team screens cardiac drugs that also attack cancer

March 14, 2016 by Jim Shelton, Yale University
Team screens cardiac drugs that also attack cancer

Several drugs now being used to treat heart failure and atrial arrhythmia also show promise as DNA disruptors in cancer cells and could be readily repurposed as anticancer agents, according to a new study by Yale researchers.

Cardiac glycosides, which are bioactive natural products found in certain plants and insects, aid in cardiac treatment because they cause the heart to contract and increase . They are used in prescription medications such as Digitoxin and Strophanthin.

Now researchers at Yale have also discovered that cardiac glycosides block the of DNA in tumor . Because are rapidly dividing, their DNA is more susceptible to damage, and inhibition of DNA repair is a promising strategy to selectively kill these cells. Several other researchers have noted that cardiac glycosides possess anticancer properties, but the basis for these effects was not well known. The Yale scientists showed that cardiac glycosides inhibit two key pathways that are involved in the repair of DNA.

"We performed a high-content drug screen with the Yale Center for Molecular Discovery, which identified some interesting cardiac drugs that affect DNA repair," said Ranjit Bindra, assistant professor of therapeutic radiology and of pathology at the Yale School of Medicine. "This has many therapeutic implications for new cancer drugs."

Bindra and Yale professor of chemistry Seth Herzon are the principal investigators of the study, which appears in the Journal of the American Chemical Society. Herzon and Bindra also are members of the Yale Cancer Center.

"Our approach focused on damaging the ' DNA using radiation, and then measuring the rate of repair in the presence of different compounds. All in all, we evaluated 2,400 compounds," Herzon said. "Surprisingly, we think that the cardiac glycosides inhibit the retention of a key DNA repair protein known as 53BP1 at the site of DNA double-strand breaks. This is a very interesting activity that was unexpected."

Herzon and Bindra said the same approach can be applied to screen hundreds of thousands of compounds. "We are partnering with industry to gain access to their large compound collections. Not only will this help us find new , it can help us elucidate more of the fundamental biology underlying DNA repair," Herzon said. The next step in their research will be to improve the cancer-fighting properties of cardiac glycosides, while modulating their other biological effects.

Explore further: Understanding the cancer-killing properties of a chemical commando

Related Stories

Heart medication converts cancer cells into vaccine

July 23, 2012

(HealthDay) -- A class of heart medications, cardiac glycosides, can induce immunogenic cell death (ICD), whereby dying cancer cells are converted into a vaccine that stimulates antitumor response, according to a study published ...

Synthetic plant hormones shut down DNA repair in cancer cells

February 16, 2016

Two drugs that mimic a common plant hormone effectively cause DNA damage and turn off a major DNA repair mechanism, suggesting their potential use as an anti-cancer therapy, say investigators at Georgetown University Medical ...

Recommended for you

On the path to an artificial cell

June 20, 2018

It is hoped that cells created in a test tube can answer some of the major questions in biology. What is the minimum that a cell needs in order to live? And how did life on Earth begin? Researchers from the Max Planck Institute ...

Novel genetic method improves efficiency of enzyme

June 20, 2018

Researchers at the U.S. Department of Energy's (DOE's) National Renewable Energy Laboratory (NREL) and the University of Georgia developed a new genetic engineering technique to dramatically improve an enzyme's ability to ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.