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Fatty acids to fight cancer
SPOKANE, Wash.—Washington State University (WSU) researchers have found a mechanism by which omega-3 fatty acids inhibit the growth and spread of prostate cancer cells. The findings, which are at odds with a 2013 study asserting that omega 3s increase the risk of prostate cancer, point the way to more effective anticancer drugs.
Scientists have long known that omega 3s reduce inflammation and have antidiabetic effects, and some recently discovered how this happens.
“But we’re the first to show that they work this way in cancer,” said Kathryn Meier, a professor of pharmacy at WSU Spokane. “The attention has mostly been on inflammation and diabetes, but there has always been an interest in cancer, and we were the first to show this mechanism in any cancer cell at all. And we’re using prostate cancer, which is the most controversial subject in omega 3s.”
A 2013 study in the Journal of the National Cancer Institute found that men with higher levels of omega-3 fatty acids in their blood had a greater risk of developing prostate cancer. It was not clear if the fatty acids came from food—certain fish, seeds and nuts are high in omega 3s—or supplements like fish oil.
Working with prostate cell cultures, Meier and two students, Ze Liu and Mandi Hopkins, found the fatty acids bind to a receptor called FFA4, for “free fatty acid receptor 4.” Rather than stimulating cancer cells, the receptor acts as a signal to inhibit growth factors, suppressing proliferation of the cancer cells.
The abstract of their paper published in the Journal of Pharmacology and Experimental Therapeutics offers this explanation:
“Omega-3 fatty acids (n-3 FAs) are proposed to have many beneficial effects on human health. However, the mechanisms underlying their potential cancer preventative effects are unclear. G protein-coupled receptors (GPCRs) of the free fatty acid receptor (FFAR) family, FFA1/GPR40 and FFA4/GPR120, specifically bind n-3 FAs as agonist ligands. In this study, we examined effects of n-3 FAs in human prostate cancer cell lines. Initial studies established that the long-chain n-3 FAs, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), inhibit proliferation of DU145 cells in response to lysophosphatidic acid (LPA), a mitogenic lipid mediator.
“When added alone to serum-starved DU145 cells, EPA transiently activates signaling events including p70S6K phosphorylation. However, when added 15 minutes prior to LPA, EPA suppresses LPA-induced activating phosphorylations of Erk, FAK and p70S6K and expression of the matricellular protein CCN1. The rapid onset of the inhibitory action of EPA suggested involvement of a GPCR.
“Further studies showed that DU145 and PC-3 cells express mRNA and protein for both FFA4 and FFA1. TUG-891, a selective agonist for FFA4, exerts inhibitory effects on LPA- and EGF-induced proliferation and migration, similar to EPA, in DU145 and PC-3 cells. The effects of TUG-891 and EPA are readily reversible. The FFA1/FFA4 agonist GW9508 likewise inhibits proliferation at doses that block FFA4. Knockdown of FFA4 expression prevents EPA- and TUG-891-induced inhibition of growth and migration. Together, these results indicate that activation of FFA4 initiates signaling events that can inhibit growth factor-induced signaling, providing a novel mechanism for suppression of cancer cell proliferation.”
“This kind of knowledge could lead us to better treat or prevent cancer because now we know how it works,” Meier said. The study also found that a drug mimicking the action of omega 3s can work as well or better than fatty acids in suppressing the cancer cells.
Meier said it is still unclear if the effect can be obtained by taking dietary supplements like fish oil. Some people don’t tolerate fish oil very well, she said. Moreover, the effect of fish oil could fade as it is digested, while data from this study suggest that an omega-3 drug needs to be in a cancer cell all the time to have an effect.
“It’s very difficult in dietary studies to tell how much to take or what form to take,” Meier said. “Should you be eating fish? Should you be taking pills? But now we have a potential drug. Once you have a drug you can test very precisely whether it works or not in a certain disease and you would know exactly how much to give people.” The drug in question, Meier relates, resulted in large part from the work done by Dr. Graeme Milligan and his collaborators in the United Kingdom. Such drugs reversibly suppress growth of the cancer cells but do not kill them, Meier notes.