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Aspirin: New insights on the 'magic drug' could help cancer patients

By Rupendra Brahambhatt,

Aspirin stock image.

Do you know every day, about 29 million people in the U.S. take the drug aspirin to overcome body pain, inflammation, and fever or to reduce the risk of a heart attack? Aspirin was chemically synthesized for the first time in 1897, and the way it affects the human body continues to surprise scientists even today.

Recently, a team of researchers from the University of Texas at Arlington (UTA) published a study that reveals new insights into how the drug works. According to the researchers, these findings hold great significance as they might lead to the development of better cancer immunotherapies and safer aspirin alternatives.

What’s more there to know about aspirin?

Aspirin contains the non-steroidal anti-inflammatory chemical acetylsalicylic acid, which is derived from a glycoside called salicin found in willow bark. About 3,500 years ago, even ancient Egyptian and Sumerians used to use willow bark to treat pain and fever.

The researchers at UTA have tried to understand the internal mechanism that allows aspirin to act as a blood-thinning agent and provide relief against inflammation, pain, and fever. One of the study authors and a biochemistry professor at UTA, Subhrangsu Mandal, shared a report with IE that explains his team’s findings in detail.

According to the report, the main findings are:

  • It is already known that aspirin inhibits the activity of the cyclooxygenase (COX) enzyme, which plays an important role in generating inflammatory responses in the human body. The study reveals that in addition to this, the drug also adversely affects the production of cell signaling proteins called cytokines, non-coding RNAs, and other pro-inflammatory genes in immune cells, which contribute to the inflammatory response in the human body.
  • During inflammation, an amino acid called tryptophan starts breaking down into its metabolite called kynurenine. This process is facilitated by an enzyme called indoleamine deoxygenase (IDO1). The study authors found that aspirin inhibits the activity of IDO1, which also acts as a target in cancer immunotherapy.
  • The study authors suggest COX also drives the IDO1 expression during an inflammatory response, and therefore it is possible that the drugs which inhibit COX could also prove to be beneficial in cancer immunotherapy.
Diagram depicting the COX-IDO interplay. Subhrangsu Mandal, University of Texas at Arlington

“We found that aspirin downregulates IDO1 expression and associated kynurenine production during inflammation. Since aspirin is a COX inhibitor, this suggests potential interplay between COX and IDO1 during inflammation,” said Professor Mandal.

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New information on aspirin will lead to new avenues

Although aspirin is frequently prescribed due to the many advantages it offers to people with inflammatory and cardiovascular conditions, the medication can also have a number of serious adverse effects.

According to the researchers, the side effects of aspirin range from an upset stomach to internal bleeding and even organ damage. Therefore, it is very important to create safer alternatives to the drug. This is where these new insights are likely to play an important role.

Based on their findings, professor Mandal and his team has already started working to develop new molecules that could modulate COX-IDO1. Hopefully, these molecules will give rise to new and more effective anti-cancer and anti-inflammatory medications.

The study will be presented at Discover BMB, the annual meeting of the American Society for Biochemistry and Molecular Biology, set to take place between March 25 to March 28, 2023, in Seattle.

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