J Cell Biochem. 2013 Jan;114(1):192-203.
EPA, an omega-3 fatty acid, induces apoptosis in human pancreatic cancer cells: role of ROS accumulation, caspase-8 activation, and autophagy induction.
Fukui M, Kang KS, Okada K, Zhu BT.
Source
Department of Pharmacology, Toxicology and Therapeutics, School of Medicine,
University of Kansas Medical Center, Kansas City, KS 66160, USA.
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.
Copyright © 2012 Wiley Periodicals, Inc.
PMID: 22903547 [PubMed - indexed for MEDLINE]