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EPA, an omega-3 fatty acid, induces apoptosis in human pancreatic cancer cells: Role of ROS accumulation, caspase-8 activation, and autophagy induction

Authors

  • Masayuki Fukui,

    1. Department of Pharmacology, Toxicology and Therapeutics, School of Medicine, University of Kansas Medical Center, Kansas City, Kansas 66160
    Current affiliation:
    1. Tropical Biosphere Research Center and Division of Host Defense and Vaccinology, Department of Microbiology, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan.
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  • Ki Sung Kang,

    1. Department of Pharmacology, Toxicology and Therapeutics, School of Medicine, University of Kansas Medical Center, Kansas City, Kansas 66160
    Current affiliation:
    1. Natural Medicine Center, Korea Institute of Science and Technology, Gangneung, Gangwon-do 210-340, Korea.
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  • Kazushi Okada,

    1. Department of Pharmacology, Toxicology and Therapeutics, School of Medicine, University of Kansas Medical Center, Kansas City, Kansas 66160
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  • Bao Ting Zhu

    Corresponding author
    1. Department of Pharmacology, Toxicology and Therapeutics, School of Medicine, University of Kansas Medical Center, Kansas City, Kansas 66160
    • Department of Pharmacology, Toxicology and Therapeutics, School of Medicine, University of Kansas Medical Center, MS-1018, Room KLSIC-4061, 2146 W. 39th Ave., Kansas City, KS 66160.
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  • Masayuki Fukui and Ki Sung Kang contributed almost equally to the work described in this study.

  • All authors have no conflict of interest to declare.

Abstract

In a recent study, we showed that eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), two common omega-3 fatty acids, can cause ROS accumulation and subsequently induce caspase-8-dependent apoptosis in human breast cancer cells (Kang et al. [2010], PLoS ONE 5: e10296). In this study, we showed that the pancreas has a unique ability to accumulate EPA at a level markedly higher than several other tissues analyzed. Based on this finding, we sought to further investigate the anticancer actions of EPA and its analog DHA in human pancreatic cancer cells using both in vitro and in vivo models. EPA and DHA were found to induce ROS accumulation and caspase-8-dependent cell death in human pancreatic cancer cells (MIA-PaCa-2 and Capan-2) in vitro. Feeding animals with a diet supplemented with 5% fish oil, which contains high levels of EPA and DHA, also strongly suppresses the growth of MIA-PaCa-2 human pancreatic cancer xenografts in athymic nude mice, by inducing oxidative stress and cell death. In addition, we showed that EPA can concomitantly induce autophagy in these cancer cells, and the induction of autophagy diminishes its ability to induce apoptotic cell death. It is therefore suggested that combination of EPA with an autophagy inhibitor may be a useful strategy in increasing the therapeutic effectiveness in pancreatic cancer. J. Cell. Biochem. 114: 192–203, 2012. © 2012 Wiley Periodicals, Inc.

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