The Epigenetics of Aspirin's Preventive Qualities

The Epigenetics of Aspirin's Preventive Qualities
October 3, 2016

What began thousands of years ago as an extract from willow bark is now a staple in American medicine cabinets. Aspirin has thrived not only on its original use as an anti-inflammatory and analgesic, but also as a commonly prescribed preventive medication for both heart disease and colorectal cancer.

AspirinEven after 5,000 years, however, aspirin is yielding new surprises. New research from Duke Health has shown that apart from its anti-inflammatory properties, aspirin has an epigenetic effect that helps to both prevent heart attacks and suppress colorectal tumors.

Dr. Deepak Voora, a cardiologist at Duke and member of Duke’s Center for Applied Genomics and Precision Medicine, followed a path of molecules the body makes in response to aspirin and found that many of these molecules are tied to DNA controls of blood platelets and tumor suppression. The paper describing this research was published in the journal EBioMedicine.

Aspirin’s primary role is to block an enzyme called COX-1. COX-1 helps the body manufacture prostaglandins, which among other things, help create inflammation. COX-1 is a common target for anti-inflammatory drugs, as ibuprofen and naproxen also block COX-1, and as COX-1 is a factor in the process of blood clotting, these drugs have a blood-thinning effect that can help prevent heart attacks.

This action against COX-1, however, does nothing to explain aspirin’s cancer-preventing effect: an effect strong enough to be recognized by the U.S. Preventive Services Task Force as beneficial for adults in their 50s.

In previous studies, Voora had found that the body responds to aspirin by turning on several genes. This set of genes creates a series of 62 small molecules that Voora named the aspirin response signature (ARS). 

In this study, Voora and his colleagues followed those ARS molecules through the blood to see what they do. They gave 53 volunteers aspirin and tested the volunteers’ blood for the genes and proteins the ARS molecules interacted with.

Sixty percent of those molecules interact with a transcription factor—a molecule that binds to and controls a specific DNA sequence—called RUNX1. 

RUNX1 is a busy molecule in the human body. RUNX1 affects megakaryocytes, the large cells found in bone marrow that create blood platelets. The ARS molecules bind with RUNX1, affecting how much is present in the body and how it promotes the production of blood platelets.

RUNX1 also plays a role in suppressing malignant tumors around the colon. The researchers in this study found an association between RUNX1 and survival without colorectal cancer.

This research, Voora says, does more than show how the preventive functions of aspirin work. The fact that ARS molecules have diverse effects on how genes get expressed shows that other medications may similarly operate epigenetically. Studying these epigenetic mechanisms for other medications could show how side effects manifest and potentially how to stop them.

Once again, one of the oldest medications in the world could have a drastic effect on the future of treating the human body.

—Daniel Lane

Daniel Lane covers science, medicine, engineering and the environment.

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