Cancer prevention Aspirin inhibits cancer-causing metabolic pathway

Causal metabolic pathway identified for the cancer-preventive effects of aspirin
It has been known for some time that the active ingredient acetylsalicylic acid ("aspirin") can prevent cancer, but so far the causative cellular processes have remained unclear, reports the German Cancer Research Center (DKFZ). Now, scientists from the DKFZ, the National Center for Tumor Diseases (NCT) Heidelberg, and the US Cancer Research Centers in Salt Lake City and Seattle have conducted a detailed analysis of the effects of aspirin on metabolism and found that aspirin controls the blood levels of a carcinogenic metabolite lowers.

Although the cancer-preventing effect of aspirin has been confirmed in several previous studies, it has not yet been possible to explain how the drug acetylsalicylic acid reduces cancer risk. In the current research, the researchers have now analyzed the cellular processes that prevent cancer from developing. They "came across a biochemical process that was not previously known to be regulated by ASA," reports the German Cancer Research Center.

Researchers have dismissed an essential aspect of the cancer-preventing effects of aspirin. (Image: Africa Studio / fotolia.com)

Mechanism of action of aspirin in cancer prevention so far unclear
According to the DKFZ, several large studies have shown that "acetylsalicylic acid (ASA) reduces the risk of colon cancer" and "possibly also reduces the risk of other cancers". However, the drug can also bring about side effects, "including sometimes severe bleeding in the gastrointestinal tract," the DKFZ continues. Therefore, before ASA can be broadly recommended for cancer prevention, researchers wanted to decipher how cancer risk is reduced. "If we know the mechanism of action, it may help us target ASA to those people who are most likely to use it and who have the least risk of developing serious side effects," explains study director Cornelia Ulrich from the Huntsman Cancer Institute, Salt Lake City.

Biochemical processes analyzed
Using the new technology of so-called "metabolite profiling", the researchers were able to identify a biochemical process that was not previously known to be regulated by ASA, reports the DKFZ. This newly discovered ASA effect could be determined by the decreasing concentration of the metabolite 2-hydroxyglutarate in the blood of the subjects. The effect was also confirmed in the investigations of two colon cancer cell lines. The metabolic product 2-hydroxyglutarate is according to the DKFZ "as a cancer driver, because in certain leukemias and brain tumors, increased concentrations of the substance were found." Currently, numerous research groups examined how 2-hydroxyglutarate drives carcinogenesis, the DKFZ.

ASA intake influences the metabolic processes
In their latest study, the researchers first evaluated the metabolic profiles of 40 subjects who had taken ASA for 60 days, with the study covering over 360 metabolites and small molecules such as sugars, amino acids or vitamins. Almost all known metabolic processes were considered according to the study leader. The scientists found that "the 2-hydroxyglutarate concentration during ASA intake fell by an average of 12 percent," according to the DKFZ. In the subsequent investigations on intestinal cancer cell lines in the culture dish, ASA even lowered the 2-hydroxyglutarate concentration by 34 percent. Further investigations showed that "ASA inhibits the enzyme HOT (hydroxyacidic oxoacid transhydrogenase), which in turn stimulates the production of 2-hydroxyglutarate," reports the DKFZ.

High potential of aspirin in cancer prevention
"The fact that we came across a cancer-relevant metabolic pathway during the investigation confirms our expectation of the potential of ASA in cancer prevention," emphasizes first author David Liesenfeld of the NCT. While previous studies of the anticancer effects of ASA have mostly focused on the anticoagulant and anti-inflammatory effects of the drug, the current "results indicate that the anticancer effect may include other mechanisms, especially at low doses." The study showed that the reduction of 2-hydroxyglutarate could also be a reason for the preventive effect, says Liesenfeld. (Fp)