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Study reveals potential mechanism for aspirin’s role in cancer prevention

It has previously been demonstrated that aspirin can decrease the risk of colorectal cancer; however, its use also carries a risk of side effects, including severe gastrointestinal bleeding.

Researchers from the Huntsman Cancer Institute in Salt Lake City (UT, USA) are now hoping to characterize the precise mechanisms of action of aspirin in low doses, before it is generally recommended as a preventative treatment.

As lead author Cornelia Ulrich of the Huntsman Cancer Institute explained: “In the long run we want to personalize prevention with aspirin because, like everything, it can have side effects. We want to be able to tailor it to people who are most likely to benefit and to have the lowest risk of adverse outcomes.”

In a study recently published in the journal Cancer Epidemiology, Biomarkers, and Prevention, Ulrich and colleagues utilized metabolite profiling to identify a biochemical pathway previously unknown to be regulated by aspirin.

The team discovered that aspirin notably decreased the level of 2-hydroxyglutarate in the blood of healthy volunteers and in two colorectal cancer cell lines. Elevated levels of 2-hydroxyglutarate have been observed in certain cancers of the blood and brain and several research groups are currently studying it as a molecule that promotes tumor formation.

The study involved the analysis of over 360 metabolites from the blood of 40 individuals who had taken aspirin for 60 days. As expected, levels of aspirin metabolites were increased in the study subjects. However, it was also discovered that there were also statistically significant decrease in the oncometabolite 2-hydroxyglutarate, which was reduced by 12% (p = 0.005).

Subsequently, the researchers evaluated the levels of 2-hydroxyglutarate in cultured colorectal cancer cells after treatment with aspirin. Consistent reductions in 2-hydroxyglutarate were found in the cultured cells, in some cases reductions of up to 34% were observed. The researchers also discovered that the primary metabolite of aspirin, salicylate, inhibits the enzyme hydroxyacidic-oxoacid transhydrogenase, which instigates the production of 2-hydroxyglutarate. This therefore suggests that aspirin is acting on a previously unknown pathway at a concentration comparable to that of individuals treated with aspirin.

“This study suggests that aspirin is playing a key role in interrupting multiple pathways that are linked to cancer development.” Ulrich commented. “Here we show both in the clinic and laboratory that a reduction in 2-hydroxyglutarate may identify a new mechanism for aspirin in cancer prevention.”

The authors state that further studies are required in order to determine whether the changes in 2-hydroyglutarate levels after aspirin treatment are also present in colon tissue.

Source: Huntsman Cancer Institute, University of Utah press release