So-called “good fatty acids” are essential for human health and are very popular with people who eat healthily. Among the omega-3 fatty acids, DHA or docosahexaenoic acid is crucial for brain function, eyesight and the regulation of inflammation.
In addition to these virtues, DHA has also been linked to reducing the incidence of cancer. How it works is the subject of an important discovery by a multidisciplinary team of researchers at the University of Leuven (UCLouvain) who have just unraveled the biochemical mechanism that enables DHA and other related fatty acids to slow the development of tumors. This is an important advance that was recently published in the prestigious journal Cell Metabolism.
Key to discovery: interdisciplinarity
In 2016, Olivier Feron’s UCLouvain team, who specialize in oncology, discovered that cells in an acidic microenvironment (acidosis) in tumors replace glucose with lipids as an energy source in order to multiply. Working with UCLouvain’s Cyril Corbet, Prof. Feron showed in 2020 that these cells are the most aggressive and acquire the ability to leave the original tumor to create metastases. Meanwhile, Yvan Larondelle, a professor in the UCLouvain Faculty of Bioengineering whose team is developing improved nutritional lipid sources, suggested to Prof. Feron that they pool their skills in a research project led by PhD student Emeline Dierge on the behavior of tumor cells in the present various fatty acids.
Thanks to the support of the Louvain Foundation, the Belgian Cancer Foundation and Telethon Télévie, the team quickly discovered that these acidotic tumor cells reacted diametrically opposite depending on the fatty acid ingested. Within a few weeks, the results were impressive and surprising. “We soon found that certain fatty acids stimulated the tumor cells while others killed them,” the researchers explained. DHA literally poisons them.
A fatal overload
The poison acts on tumor cells through a phenomenon called ferroptosis, a type of cell death associated with the peroxidation of certain fatty acids. The greater the amount of unsaturated fatty acids in the cell, the greater the risk of their oxidation. Normally, cells in the acidic compartment of tumors store these fatty acids in lipid droplets, a kind of bundle in which fatty acids are protected from oxidation. In the presence of a large amount of DHA, however, the tumor cell is overwhelmed and cannot store the DHA, which oxidizes and leads to cell death. By using a lipid metabolism inhibitor that prevents the formation of lipid droplets, the researchers observed that this phenomenon is exacerbated, confirming the identified mechanism and opening the door to combined treatment options.
For their study, the UCLouvain researchers used a 3D tumor cell culture system called spheroids. In the presence of DHA, spheroids grow first and then implode. The team also fed a DHA-enriched diet to mice with tumors. The result: Tumor development was significantly slowed compared to mice with a conventional diet.
This UCLouvain study shows the value of DHA in fighting cancer. “For an adult,” according to the UCLouvain researchers, “it is recommended to consume at least 250 mg DHA per day. However, studies show that our diet only provides 50 to 100 mg per day on average. This is well below the recommended minimum dose. “
Reference: E. Dierge, E. Debock, C. Guilbaud et al. The peroxidation of n-3 and n-6 polyunsaturated fatty acids in the acidic tumor environment leads to ferroptosis-mediated anti-cancer effects. Cell metab. 2021. doi: 10.1016 / j.cmet.2021.05.016
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