Inhibition of PC3 human prostate cancer cell proliferation, invasion and migration by eicosapentaenoic acid and docosahexaenoic acid

Abstract

Abstract. The n-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), found in fish oil, exert a number of beneficial effects, and they are used in the treatment of hyperlipidemia. In recent years, EPA and DHA have been found to affect cancer cell proliferation. In the present study, PC3 cells, which are androgen-independent prostate cancer cells that resemble castration-resistant prostate cancer cells, were used to investigate a possible novel treatment for castration-resistant prostate cancer. The PC3 cells were cultured and incubated with various concentrations of EPA or DHA. Cancer proliferation was confirmed by trypan blue microscopy. Invasion and migration assays were used in the upper chamber in PC3 cells, and serum-free medium and various concentrations of EPA or DHA were placed in the lower chamber in serum-containing medium. EPA and DHA decreased PC3 cell proliferation, invasion and migration. The effect of EPA on PC3 cells was dose-dependent and significant differences were observed at concentrations of 100 and 200 µg/ml. The effect of DHA on PC3 cells was similar to that of EPA. In the migration assay, EPA exerted almost no effects at 25 µg/ml, but migration was reduced at 50 µg/ml. Similar to EPA, DHA exerted almost no effects at 25 µg/ml, but further reduction was observed at the 50 µg/ml concentration. In the invasion assay, EPA at 25 µg/ml was not significantly different from the control, but suppressed invasion at 50 µg/ml. DHA decreased invasion compared with the control at 25 µg/ml, whereas invasion was significantly reduced at a DHA concentration of 50 µg/ml. In conclusion, it was demonstrated that EPA and DHA were effective in decreasing the proliferation, invasion and migration of prostate PC3 cancer cells. However, the detailed underlying mechanisms have not yet been fully elucidated. IntroductionEicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are n-3 fatty acids that have several beneficial effects, including decreasing the plasma triglyceride concentration, lipoprotein metabolism (1,2), inhibiting platelet aggregation by collagen (3), and improving the reduced elasticity of the arterial walls through the endothelium-dependent relaxation response in rabbits (4). For these reasons, DHA and EPA are clinically used in Japan. In recent years, n-3 fatty acids have been shown to decrease the proliferation of cancer cells in colon, breast and liver cancer, as well as neuroblastoma. In addition, n-3 fatty acids may be used in cancer cachexia; the combination of chemotherapy and n-3 fatty acids was helpful in the curative as well as the palliative clinical setting (5), but a systematic review did not evaluate the balance of their cost-effectiveness against their utility (6). A number of studies have investigated cancer cell growth; however, only a limited number of studies have examined invasion and metastasis in prostate cancer, which exhibits an increasing prevalence. In the present study, the PC3 prostate cancer cell line was used, which is an androgen-independen...

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