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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.
J Cell Biochem 2013; 114(1):192-203JC

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.

Authors+Show Affiliations

Department of Pharmacology, Toxicology and Therapeutics, School of Medicine, University of Kansas Medical Center, Kansas City, KS 66160, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22903547

Citation

Fukui, Masayuki, et al. "EPA, an Omega-3 Fatty Acid, Induces Apoptosis in Human Pancreatic Cancer Cells: Role of ROS Accumulation, Caspase-8 Activation, and Autophagy Induction." Journal of Cellular Biochemistry, vol. 114, no. 1, 2013, pp. 192-203.
Fukui M, Kang KS, Okada K, et al. EPA, an omega-3 fatty acid, induces apoptosis in human pancreatic cancer cells: role of ROS accumulation, caspase-8 activation, and autophagy induction. J Cell Biochem. 2013;114(1):192-203.
Fukui, M., Kang, K. S., Okada, K., & Zhu, B. T. (2013). EPA, an omega-3 fatty acid, induces apoptosis in human pancreatic cancer cells: role of ROS accumulation, caspase-8 activation, and autophagy induction. Journal of Cellular Biochemistry, 114(1), pp. 192-203. doi:10.1002/jcb.24354.
Fukui M, et al. EPA, an Omega-3 Fatty Acid, Induces Apoptosis in Human Pancreatic Cancer Cells: Role of ROS Accumulation, Caspase-8 Activation, and Autophagy Induction. J Cell Biochem. 2013;114(1):192-203. PubMed PMID: 22903547.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - EPA, an omega-3 fatty acid, induces apoptosis in human pancreatic cancer cells: role of ROS accumulation, caspase-8 activation, and autophagy induction. AU - Fukui,Masayuki, AU - Kang,Ki Sung, AU - Okada,Kazushi, AU - Zhu,Bao Ting, PY - 2012/07/18/received PY - 2012/08/07/accepted PY - 2012/8/21/entrez PY - 2012/8/21/pubmed PY - 2013/4/23/medline SP - 192 EP - 203 JF - Journal of cellular biochemistry JO - J. Cell. Biochem. VL - 114 IS - 1 N2 - 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. SN - 1097-4644 UR - https://www.unboundmedicine.com/medline/citation/22903547/EPA_an_omega_3_fatty_acid_induces_apoptosis_in_human_pancreatic_cancer_cells:_role_of_ROS_accumulation_caspase_8_activation_and_autophagy_induction_ L2 - https://doi.org/10.1002/jcb.24354 DB - PRIME DP - Unbound Medicine ER -