Researchers may have identified a new mechanism for aspirin in cancer prevention, according to findings from a study published in Cancer Epidemiology, Biomarkers, and Prevention

Previously, aspirin has been shown to reduce the risk of colorectal cancer and other cancers.  Cornelia Ulrich, PhD, Senior Director of Population Sciences at Huntsman Cancer Institute in Salt Lake City, and colleagues conducted a study to better understand the mechanisms of aspirin at low doses “before recommending it more generally as a preventative.” They used metabolite profiling to identify a novel biochemical pathway regulated by aspirin. They found that aspirin substantially decreases the level of 2-hydroxyglutarate, an oncometabolite, in the blood of healthy volunteers and in two colorectal cancer cell lines. High levels of 2-hydroxyglutarate have been detected in certain blood and brain cancers. 

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For the first part of the study, study authors examined metabolic profiles from the blood of 40 patients who had taken aspirin for 60 days. Over 360 metabolites were analyzed covering most of the body’s known biochemical pathways. They found that aspirin metabolites were higher in the volunteers as expected (P<0.001) but a statistically significant 12% reduction in the oncometabolite 2-hydroxyglutarate (P=0.005) was observed.

The researchers then evaluated 2-hydroxyglutarate levels in cultured cancer cells after treatment with aspirin. Up to 34% reductions of 2-hydroxyglutarate were seen in the colorectal cell lines. Salicylate, the main metabolite of aspirin, was found to inhibit an enzyme called HOT (hydroxyacidic-oxoacid transhydrogenase) that triggers the production of 2-hydroxyglutarate. This suggested that aspirin was acting on an unknown pathway at a concentration similar to that of individuals treated with aspirin. 

Study findings support the overall importance of aspirin in cancer prevention and brings to light a new pathway that warrants further research in the context of aspirin. More studies will be needed to determine whether changes in 2-hydroxyglutarate levels are also seen in colon tissue. 

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