Tumours poisoned by omega-3

Tumours that explode under the effect of a polyunsaturated fatty acid, DHA: this is what researchers from UCLouvain have observed and explained. Their results are published in the journal Cell Metabolism and create possibilities for prevention and combined treatment in fighting cancer.

Omega-3 polyunsaturated fatty acids are essential to the body’s proper functioning. These “good fatty acids” are sought after by people who try to eat healthily. However, consuming these fatty acids is often not enough and some people turn to food supplements.

Among omega-3 fatty acids, docosahexaenoic acid, or DHA, has a special place owing to its importance to brain function, vision and the regulation of inflammatory phenomena. In addition, DHA has also been associated with a reduction in the incidence of cancer. This property is the subject of a recent important discovery: the biochemical mechanism that allows DHA and other related fatty acids to slow the development of tumours has recently been elucidated by a multidisciplinary team of UCLouvain researchers. This is a major advance that has just been published in the prestigious journal Cell Metabolism.

In 2016, Olivier Feron’s team (IREC), specialising in oncology, discovered that cells in an acidic microenvironment (acidosis) within tumours replace glucose with lipids as an energy source in order to multiply. In 2020, in collaboration with Cyril Corbet (IREC), Prof. Feron demonstrated that these same cells are the most aggressive and acquire the ability to leave the original tumour to generate metastases. In parallel, Yvan Larondelle (LIBST), whose team is developing improved dietary lipid sources, proposed to Prof. Feron that they combine their skills to launch a research project, led by PhD student Emeline Dierge, to evaluate the behaviour of tumour cells in the presence of different fatty acids. Thanks to the support of the Louvain Foundation, the Belgian Cancer Foundation and the Télévie telethon, the team quickly determined that tumour cells in acidosis respond in diametrically opposed ways depending on the fatty acid they absorb. Within a few weeks, the results were both impressive and surprising! “We soon found that some fatty acids stimulated the tumour cells while others killed them!" the researchers explain. Thus the DHA poisons them to death.

How does this poison act on tumour cells? By involving a phenomenon called ferroptosis, a type of cell death linked to the peroxidation of certain fatty acids. The more unsaturated fatty acids in the cell, the greater the risk of their oxidation. Normally, in the acidic compartment of tumours, the cells store these fatty acids in lipid droplets, a kind of bundle in which the 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, the researchers were able to observe that this phenomenon is further amplified, which confirms the identified mechanism and creates possibilities for combined treatment.

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

This UCLouvain study shows the value of DHA in fighting cancer. “For an adult,” the researchers stated, “it’s recommended to take at least 250 mg of DHA per day. However, studies show that our diet provides us on average with only 50 to 100 mg per day. This is well below the minimum recommended intake.”

In what foods is it found? In certain microalgae, in cold-water fish such as properly fed trout and salmon, or in the eggs of chicken whose diet is optimised (up to 100 mg of DHA/egg). The researchers conclude, “The challenge is to produce these foods without contamination by environmental pollutants, which is quite possible in some areas in Belgium and especially the Walloon Region. In this respect, the establishment of differentiated quality chains that give pride of place to DHA should be encouraged.”