SWATH differential abundance proteomics and cellular assays show in vitro anticancer activity of arachidonic and docosahexaenoic acid monoacylglycerols in HT-29 colorectal cancer cell line

Colorectal cancer (CRC) is one of the most common and mortal types of cancer. There is increasing evidence that some polyunsaturated fatty acids (PUFA) exercise specific inhibitory actions on cancer cells through different mechanisms, as a previous study on the effect on CRC cells of two PUFA free fatty acids (FFA), docosahexaenoic acid (DHA, 22:6n3) and arachidonic acid (ARA, 20:4n6)-FFA, shown. Here we have used the same study design and technology to investigate the actions of DHA and ARA-monoacylglycerols (MAG), and we have compared the results with the previous study of the corresponding FFA. Cell assays revealed that ARA- and DHA-MAG exercised dose- and time-dependent antiproliferative actions, with DHA-MAG acting on cancer cells more efficiently than ARA-MAG. SWATH-MS massive quantitative proteomics, validated by parallel reaction monitoring and followed by pathway analysis, revealed that DHA-MAG had a massive effect in the proteasome complex, while ARA-MAG main effect was related to DNA replication. Prostaglandin synthesis also resulted inhibited by DHA-MAG. Results clearly demonstrated the ability of MAGs to induce cell death in colon cancer cells and suggested a direct relationship between chemical structure and effect.