Researchers revealed a pathway in cell culture and mice by which salicylic acid decreases inflammation and by which salicylic acid and diflunisal decrease cancerous growth. Salicylic acid is an important active metabolite of acetylsalicylic acid, better known as aspirin. Diflunisal is a derivative of salicylic acid and a potent analog of aspirin.1
“Salicylic acid is one of the oldest drugs on the planet, dating back to the Egyptians and the Greeks, but we’re still discovering new things about it,” said Eric Verdin, MD, associate director of the J. David Gladstone Institute of Virology and Immunology, San Francisco, California, and senior author of the study.
“Uncovering this pathway of inflammation that salicylic acid acts upon opens up a host of new clinical possibilities for these drugs.”
This study, published in eLife, showed that salicylic acid and diflunisal suppressed 2 proteins, CREB-binding protein (CBP) and p300, which function to modulate gene expression throughout the body. CBP and p300 are involved in cellular growth or regulate the levels of inflammatory proteins. By suppressing these proteins, salicylic acid and diflunisal prevent cellular damage caused by inflammation.
Previous research described a connection between p300 and AML1-ETO, a leukemia-promoting protein. This study showed that using diflunisal to suppress p300 in cell culture and mouse models of leukemia inhibited growth of the disease and shrank tumors.
“The ability to repurpose drugs that are already FDA-approved to be part of novel therapies for cancer patients is incredibly exciting,” said the study’s co-author Stephen Nimer, MD. a leukemia treatment specialist at the University of Miami, Miami, Florida.
“We have conducted a clinical trial of salicylic acid in patients with hematologic cancers and found it to be safe. Thus, this collaborative effort to develop novel epigenetic therapies is an important next step in our journey to find more effective treatment for leukemia patients.”
The researchers are hoping to establish a clinical trial to test the ability of salicylic acid to treat patients with leukemia in combination with other therapies.
1. Shirakawa K, Wang L, Man N, et al. Salicylate, diflunisal and their metabolites inhibit CBP/p300 and exhibit anticancer activity [published online May 31, 2016]. eLife. doi:10.7554/eLife.11156.