An omega-3 fatty acid kills tumor by ferroptosis

So-called "good fatty acids" are essential for human health and much sought after by those who try to eat healthily. Among the Omega-3 fatty acids, DHA or docosahexaenoic acid is crucial to brain function, vision and the regulation of inflammatory phenomena.

In addition to these virtues, DHA is also associated with a reduction in the incidence of cancer. How it works is the subject of a major discovery by a multidisciplinary team of researchers, who have just elucidated the biochemical mechanism that allows DHA and other related fatty acids to slow the development of tumours. This is a major advance that has recently been published in the prestigious journal Cell Metabolism.

In 2016, the team, which specialises in oncology, discovered that cells in an acidic microenvironment (acidosis) within tumors replace glucose with lipids as an energy source in order to multiply. In 2020 the team demonstrated that these same cells are the most aggressive and acquire the ability to leave the original tumour to generate metastases.

The team quickly identified that these acidotic tumour cells responded in diametrically opposite ways depending on the fatty acid they were absorbing. Within a few weeks, the results were both impressive and surprising. "We soon found that certain fatty acids stimulated the tumour cells while others killed them," the researchers explained. DHA literally poisons them.

The poison acts on tumour cells via a phenomenon called ferroptosis, a type of cell death linked to 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, in the acidic compartment within tumours, cells store these fatty acids in lipid droplets, a kind of bundle in which fatty acids are protected from oxidation. But in the presence of a large amount of DHA, the tumour cell is overwhelmed and cannot store the DHA, which oxidises and leads to cell death. By using a lipid metabolism inhibitor that prevents the formation of lipid droplets, researchers were able to observe that this phenomenon is further amplified, which confirms the identified mechanism and opens the door to combined treatment possibilities.

For their study, the researchers used a 3D tumour cell culture system, called spheroids. In the presence of DHA, spheroids first grow and then implode. The team also administered a DHA-enriched diet to mice with tumours. The result: tumour development was significantly slowed compared to that in mice on a conventional diet.

This study shows the value of DHA in fighting cancer. "For an adult," the researchers stated, "it's recommended to consume at least 250 mg of DHA per day. But studies show that our diet provides on average only 50 to 100 mg per day. This is well below the minimum recommended intake."

https://uclouvain.be/en/discover/press/news/an-omega-3-that-s-poison-for-tumours.html

https://www.cell.com/cell-metabolism/fulltext/S1550-4131(21)00233-3