So-called "good fatty acids" are
essential for human health. 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 University of
Louvain (UCLouvain) researchers, who have just elucidated the biochemical
mechanism that allows DHA and other related fatty acids to slow the development
of tumors. This is a major advance that has recently been published in the
prestigious journal Cell Metabolism.
Key
to the discovery: interdisciplinarity
In 2016, Olivier Feron's UCLouvain team,
which specializes 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 collaboration with UCLouvain's Cyril
Corbet, Prof. Feron demonstrated in 2020 that these same cells are the most
aggressive and acquire the ability to leave the original tumor to generate
metastases. Yvan Larondelle, a professor in the UCLouvain Faculty of
Bioengineering, whose team is developing improved dietary lipid sources,
proposed to Prof. Feron that they combine their skills in a research project,
led by Ph.D. candidate Emeline Dierge, to evaluate the behavior of tumor cells
in the presence of fatty acids.
The team quickly identified that these
acidotic tumor cells responded in diametrically opposite ways depending on the
fatty acid they were absorbing. 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.
3D tumors that disintegrate within a few
days thanks to the action of a well-known Omega-3 (DHA, found mainly in fish)
-- this is the exceptional discovery by University of Louvain.Hungry for fatty
acids, tumor cells in acidosis gorge themselves on DHA but are unable to store
it correctly and literally poison themselves. The result? They die. Credit:
Copyright UCLouvain
A
fatal overload
The poison acts on tumor 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 tumors, 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 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, 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, UCLouvain researchers used
a 3D tumor 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 tumors. The result: tumor development was significantly
slowed compared to that in mice on a conventional diet.
This UCLouvain study shows the value of DHA
in fighting cancer. "For an adult," the UCLouvain 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."