Contribution of Pyk2 pathway and reactive oxygen species (ROS) to the anti-cancer effects of eicosapentaenoic acid (EPA) in PC3 prostate cancer cells

Abstract

Background n-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. Objective We investigated the anti-cancer effects and mechanism of action of EPA on PC3 prostate cancer cells in vitro. Methods PC3 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. Results EPA 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. Conclusions Inhibition of Pyk2 phosphorylation and ROS production contribute to the anticancer effects of EPA on PC3 cells.

Unraveling the Metabolic Alterations Induced by Zika Infection in Prostate Epithelial (PNT1a) and Adenocarcinoma (PC-3) Cell Lines

“…It inhibits the phosphorylation of proline-rich tyrosine kinases (PYK2) and ERK and induces overproduction of ROS, exerting antiproliferative effects in PC-3. This anticancer effect has been pointed out by Oono et al as dose-dependent, decreasing PC-3 cell proliferation, migration, and invasion . Consistent with a potential increase of the ROS species, we observed a significant decrease in the antioxidant molecule glutathione (log 2 FC = −3.02, p -value < 0.05) in PC-3 ZIKV-infected cells, while this marker was not even detected in PNT1a.…”

“…This anticancer effect has been pointed out by Oono et al as dose-dependent, decreasing PC-3 cell proliferation, migration, and invasion. 38 Consistent with a potential increase of the ROS species, we observed a significant decrease in the antioxidant molecule glutathione (log 2 FC = −3.02, p-value < 0.05) in PC-3 ZIKVinfected cells, while this marker was not even detected in PNT1a. The reduction of antioxidants may lead to apoptosis signaling.…”

Docosahexaenoic acid inhibits vascular smooth muscle cell migration and proliferation by decreasing microRNA‑155 expression levels

“…in the present study, the protective mechanism of dHa in the inhibition of VSMc proliferation and migration was investigated. Previous studies on the protective effect of dHa in cardiovascular diseases focused on changes in gene expression (29,30). The present study demonstrated that the inhibitory effect of dHa on the proliferation and migration of VSMcs is mediated by microrna-155 downregulation.…”

Fatty Acid Composition and Cytotoxic Activity of Lipid Extracts from Nannochloropsis gaditana Produced by Green Technologies

“…Additionally, in a first attempt to understand the cytotoxicity mechanism of the microalgal extracts in the tumorigenic cells, the effect of omega-3 lipid extracts on cellular ROS levels of HCT-116 cells was investigated with the DCF assay (Figure 6). Different studies have shown that the accumulation of certain PUFAs leads to increased lipid peroxidation and the generation of intracellular radical species that may be toxic to cancer cells [42,47,49,50]. However, in this study and under the conditions tested, the incubation of HCT-116 cells with the microalgal lipid extract did not result in a significant increase in intracellular ROS levels regardless of the concentration or type of extract used (p > 0.05).…”