This remarkable discovery by researchers at the University of Louvain (UC Louvain) reveals that 3D tumors disintegrate within days, thanks to the effects of a well-known omega-3 fatty acid, DHA, primarily found in fish. Cancerous cells in acidosis exhibit a voracious appetite for fatty acids, ingesting large amounts of DHA but failing to store it properly, ultimately poisoning themselves. The result? Their demise.

Dubbed the "good fatty acid," DHA is crucial for human health and sought after by those striving for a healthier diet. Among Omega-3 fatty acids, DHA, or docosahexaenoic acid, is vital for brain function, vision, and the regulation of inflammatory processes.

Beyond these benefits, DHA also demonstrates the potential to reduce cancer incidence. How it works is the subject of a groundbreaking discovery by a multidisciplinary team of researchers at UC Louvain, who have just elucidated the biochemical mechanisms by which DHA and other related fatty acids slow down tumor progression. This significant advancement was recently published in the prestigious journal Cell Metabolism.

The Key to the Discovery: Interdisciplinarity

In 2016, Olivier Feron's tumor research team at UC Louvain discovered that cells within the acidic microenvironment (acidosis) of tumors replace glucose with lipids as an energy source for proliferation. Collaborating with Cyril Corbet from UC Louvain, Professor Feron demonstrated in 2020 that these cells are the most aggressive and possess the ability to leave the primary tumor and generate metastases. Meanwhile, Professor Yvan Larondelle from UC Louvain's Bioengineering Institute, whose team was developing improved dietary lipid sources, proposed to Professor Feron that they combine their expertise in a research project led by doctoral student Emilie Dierge to assess tumor cell behavior in response to different fatty acids.

Supported by the Louvain Foundation, the Belgian Foundation Against Cancer, and Télévie, the research group swiftly discovered that these acidic tumor cells responded in starkly contrasting ways depending on the fatty acids they absorbed. Within weeks, the results were both impressive and surprising. "We quickly found that certain fatty acids stimulated cancer cells, while others killed them," explained the researchers. DHA proved to be the latter.

A Deadly Overload

This toxicity works through a phenomenon called ferroptosis, a type of cell death associated with the peroxidation of certain fatty acids. The more unsaturated fatty acids a cell contains, the greater the risk of oxidation. Normally, in the acidic chambers of tumors, cells store these fatty acids in lipid droplets, which act as protective bundles shielding them from oxidation. However, in the presence of abundant DHA, tumor cells become overwhelmed and unable to store it, leading to oxidation and subsequent cell death. By using lipid metabolism inhibitors to prevent lipid droplet formation, researchers observed this phenomenon being further amplified, confirming the established mechanism and opening doors for combination therapies.

In their study, UC Louvain researchers employed a 3D tumor cell culture system called spheroids. In the presence of DHA, the spheroids initially grew before imploding. The team also fed mice with tumors a DHA-rich diet. The result: tumor development significantly slowed compared to mice on a regular diet.

UC Louvain's research underscores the anticancer value of DHA. "For adults," say UC Louvain researchers, "it is recommended to consume at least 250 mg of DHA daily." However, studies show that our diets average only 50 to 100 mg per day, far below the minimum recommended intake."