Abstract
Backgroundn-3 polyunsaturated fatty acids (n-3 PUFAs), including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are thought to exert protective effects in cardiovascular diseases. In addition, n-3 PUFAs have demonstrated anti-cancer effects in vitro and in vivo.ObjectiveWe investigated the anti-cancer effects and mechanism of action of EPA on PC3 prostate cancer cells in vitro.MethodsPC3 cells were treated with various concentrations of EPA, and cell survival and the abilities of migration and invasion were evaluated. The time course of the growth inhibitory effect of EPA on PC3 cells was also assessed. The mechanism underlying the anti-cancer effects of EPA was investigated by human phosphokinase and human apoptosis antibody arrays, and confirmed by western blot analysis. We also examined the contribution of reactive oxygen species (ROS) to the effects of EPA using the ROS inhibitor N-acetyl cysteine.ResultsEPA decreased the survival of PC3 cells in a dose-dependent manner within 3 h of application, with an effective concentration of 500 μmol/L. EPA inhibited proline-rich tyrosine kinase (Pyk)2 and extracellular signal-regulated kinase 1/2 phosphorylation as determined by western blotting and the antibody arrays. The growth of PC3 cells was inhibited by EPA, which was dependent on ROS induction, while EPA inhibited Pyk2 phosphorylation independent of ROS production.ConclusionsInhibition of Pyk2 phosphorylation and ROS production contribute to the anticancer effects of EPA on PC3 cells.
Highlights
Prostate cancer (PC) is the second most common cancer in men worldwide, with the incidence increasing in Asian countries, including Japan [1, 2]
eicosapentaenoic acid (EPA) suppresses PC3 cell proliferation EPA inhibited the proliferation of PC3 cells in a dosedependent manner (Fig. 1)
In serum-free medium, the number of PC3 cells in the control group did not change over a 24-h period, but gradually decreased with EPA treatment, with significant differences detected after 3 h
Summary
Prostate cancer (PC) is the second most common cancer in men worldwide, with the incidence increasing in Asian countries, including Japan [1, 2]. Profiles, prevent the progression of atherosclerosis, and reduce the incidence of cardiovascular diseases [7] as well as liver and plasma triglyceride levels [8]. N-3 PUFAs have been reported to have various anti-cancer effects in several types of malignancy in vitro and in vivo. N-3 PUFAs inhibit extracellular signal-regulated kinase (ERK) and Akt signaling pathways and show anti-cancer effects in breast cancer [10], reduce the incidence of liver cancer in hepatitis virus-infected patients [11], and lower the risk of pancreatic cancer [12]. Other studies have suggested that there is insufficient evidence for a significant association between n-3 PUFAs and cancer incidence [17]
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