Omega-3 fatty acids can act through a host receptor, GPR120, to confer anticancer effects in prostate malignancies, according to a study published in the Journal of the National Cancer Institute.1 GPR120, also known as FFA4, is a G protein–coupled receptor that binds long chain polyunsaturated fatty acids, such as omega-3 fatty acids.
“This is a nice step,” Kathryn Meier, PhD, professor of pharmaceutical sciences at Washington State University, Spokane, told CTA. She wrote a corresponding editorial, but was not involved in the original study.2 The study builds on previous research from Dr Meier and colleagues that showed omega-3 fatty acids and synthetic GPR120 agonists had anticancer effects on human prostate cancer cells. “It’s 1 more piece in the puzzle.”
The aim of the current study was to determine the role of host compared with tumor GPR120 in mediating the benefits of omega-3 fatty acids. To do so, wild-type and GPR120-knockout mice were first injected with a prostate cancer cell line. Once tumors grew to 30 mm3 to 50 mm3, mice were assigned to a diet that was either fish oil- (omega-3) or corn oil-(omega-6) based. The corn oil diet served as a control group to mimic the American diet.
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Wild-type mice fed a fish-oil diet had slowed tumor growth and smaller final tumor volume compared with those fed corn oil (P = .04). As for GPR120 knockout mice, no difference in tumor growth rate or final tumor volume was seen between diet groups.
The researchers also assessed whether omega-3 fatty acids act on tumor-associated macrophages (TAMs) via the GPR120 receptor. Most TAMs in prostate cancer are M2, a subtype that favors tumor progression. Decreased quantities of M2-like TAMs and expression of M2 markers in isolated TAMs were found in wild-type mice fed a diet based on fish oil. This effect on immune cells was not observed in GPR120-knockout mice.
Lastly, the researchers measured GPR120 gene expression, cell cycle progression genes, and Ki67 (a marker for cell proliferation) in archived human prostate tumor samples procured from a trial in which fish oil was the intervention. The researchers found that higher GPR120 gene expression was associated with lower expression of cell cycle progression genes in samples from men who consumed a diet high in fish oil.
“Since the tumor microenvironment is composed of immune cells from the host, and the immune system is very important to tumor growth, we conclude that GPR120, possibly in the host immune system, is necessary for the anticarcinogenic effect of fish oil,” senior study author William Aronson, MD, told Cancer Therapy Advisor.Dr Aronson is a professor in the department of urology at the University of California Los Angeles. “Possibly, we will be able to favorably modify the host immune system with fish oil to benefit prostate cancer patients. Medication that also affects the GPR120 receptor may also have favorable effects as well.”
Plans are already underway to build upon these findings. “We received funding from NIH to further investigate the role of the host immune system on the anticarcinogenic activity of fish oil affecting the immune system,” Dr Aronson said.
The group also has an ongoing study in men on active surveillance for prostate cancer in which participants are randomized to receive fish oil plus a low corn oil diet or plus their usual diet without fish oil supplements. “It is our hypothesis that men with higher gene expression of GPR120 in the prostate will benefit more from the fish oil diet,” Dr Aronson said. “This might lead to personalized nutritional intervention treatments for patients with prostate cancer.”
References
- Liang P, Henning SM, Guan J, et al. Role of host GPR120 in mediating dietary omega-3 fatty acid inhibition of prostate cancer[published online September 6, 2018]. J Natl Cancer Inst. doi: 10.1093/jnci/djy125
- Meier KE. Omega-3 fatty acids and prostate cancer: G protein–coupled receptors to the rescue[published online September 6, 2018]. J Natl Cancer Inst. doi: 10.1093/jnci/djy127
