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 i...

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Main Authors: Keiichi Oono, Kazuo Ohtake, Chie Watanabe, Sachiko Shiba, Takashi Sekiya, Keizo Kasono
Format: Article
Language:English
Published: BMC 2020-01-01
Series:Lipids in Health and Disease
Subjects:
Online Access:https://doi.org/10.1186/s12944-019-1122-4
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author Keiichi Oono
Kazuo Ohtake
Chie Watanabe
Sachiko Shiba
Takashi Sekiya
Keizo Kasono
author_facet Keiichi Oono
Kazuo Ohtake
Chie Watanabe
Sachiko Shiba
Takashi Sekiya
Keizo Kasono
author_sort Keiichi Oono
collection DOAJ
description 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.
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spelling doaj.art-f30a32656ac547a88675762458f1d6562022-12-21T20:29:53ZengBMCLipids in Health and Disease1476-511X2020-01-0119111210.1186/s12944-019-1122-4Contribution of Pyk2 pathway and reactive oxygen species (ROS) to the anti-cancer effects of eicosapentaenoic acid (EPA) in PC3 prostate cancer cellsKeiichi Oono0Kazuo Ohtake1Chie Watanabe2Sachiko Shiba3Takashi Sekiya4Keizo Kasono5Laboratory of Physiology, Faculty of Pharmaceutical Sciences, Josai UniversityLaboratory of Physiology, Faculty of Pharmaceutical Sciences, Josai UniversityLaboratory of Clinical Pathology, Faculty of Pharmaceutical Sciences, Josai UniversityLaboratory of Physiology, Faculty of Pharmaceutical Sciences, Josai UniversityLaboratory of Clinical Pathology, Faculty of Pharmaceutical Sciences, Josai UniversityLaboratory of Physiology, Faculty of Pharmaceutical Sciences, Josai UniversityAbstract 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.https://doi.org/10.1186/s12944-019-1122-4PC3EPAROSERKPyk2
spellingShingle Keiichi Oono
Kazuo Ohtake
Chie Watanabe
Sachiko Shiba
Takashi Sekiya
Keizo Kasono
Contribution of Pyk2 pathway and reactive oxygen species (ROS) to the anti-cancer effects of eicosapentaenoic acid (EPA) in PC3 prostate cancer cells
Lipids in Health and Disease
PC3
EPA
ROS
ERK
Pyk2
title Contribution of Pyk2 pathway and reactive oxygen species (ROS) to the anti-cancer effects of eicosapentaenoic acid (EPA) in PC3 prostate cancer cells
title_full Contribution of Pyk2 pathway and reactive oxygen species (ROS) to the anti-cancer effects of eicosapentaenoic acid (EPA) in PC3 prostate cancer cells
title_fullStr Contribution of Pyk2 pathway and reactive oxygen species (ROS) to the anti-cancer effects of eicosapentaenoic acid (EPA) in PC3 prostate cancer cells
title_full_unstemmed Contribution of Pyk2 pathway and reactive oxygen species (ROS) to the anti-cancer effects of eicosapentaenoic acid (EPA) in PC3 prostate cancer cells
title_short Contribution of Pyk2 pathway and reactive oxygen species (ROS) to the anti-cancer effects of eicosapentaenoic acid (EPA) in PC3 prostate cancer cells
title_sort contribution of pyk2 pathway and reactive oxygen species ros to the anti cancer effects of eicosapentaenoic acid epa in pc3 prostate cancer cells
topic PC3
EPA
ROS
ERK
Pyk2
url https://doi.org/10.1186/s12944-019-1122-4
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