Abstract
Colorectal cancer (CRC) is one of the most common and mortal types of cancer. There is increasing evidence that some polyunsaturated fatty acids (PUFAs) exercise specific inhibitory actions on cancer cells through different mechanisms, as a previous study on CRC cells demonstrated for two very long-chain PUFA. These were docosahexaenoic acid (DHA, 22:6n3) and arachidonic acid (ARA, 20:4n6) in the free fatty acid (FFA) form. In this work, similar design and technology have been used to investigate the actions of both DHA and ARA as monoacylglycerol (MAG) molecules, and results have been compared with those obtained using 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. Sequential window acquisition of all theoretical mass spectra (SWATH)—mass spectrometry 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 the ARA-MAG main effect was related to DNA replication. Prostaglandin synthesis also resulted as inhibited by DHA-MAG. Results clearly demonstrated the ability of both ARA- and DHA-MAG to induce cell death in colon cancer cells, which suggests a direct relationship between chemical structure and antitumoral actions.
Highlights
The fat content of a normal diet consists mainly of triacylglycerols (TAG) and small amounts of sterols and phospholipid esters, as well as fat-soluble vitamins (A, D, E, and K) [1]
In a previous study focused on Free fatty acid (FA) (FFA), we demonstrated that docosahexaenoic acid (DHA)-FFA inhibited HT-29 cells proliferation to a higher extent than
DHASCO® (40% DHA, a mixture of the oil extracted from the unicellular alga Crypthecodinium cohnii and high oleic sunflower oil) and ARASCO® (40% arachidonic acidacid (ARA), a mixture of an oil extracted from the unicellular fungi Mortierella alpina and high oleic sunflower oil) oils were supplied by Martek Bioscience
Summary
The fat content of a normal diet consists mainly of triacylglycerols (TAG) (about 90% of total ingested lipids) and small amounts of sterols and phospholipid esters, as well as fat-soluble vitamins (A, D, E, and K) [1]. The fatty acid (FA) distribution on the glycerol backbone of TAG influences their absorption, distribution, and tissue uptake [2]. Free FA (FFA) and sn-2-monoacylglycerol (sn-2 MAG), the two hydrolysis products of dietary TAG, are absorbed from the lumen into polarized enterocytes in the small intestine. Polyunsaturated FAs (PUFAs) are better absorbed when they are esterified at the sn-2 position of the glycerol molecule, while the type of FA at the remaining locations influences their intestinal absorption [2,3,4,5]. Arachidonic acid (ARA, 20:4n6) is a long-chain PUFA (LCPUFA) belonging to the n-6 family. This molecule is the precursor of the biosynthetic pathway leading to the production of prostaglandin
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