Omega-3 Fatty Acids mediate immune regulation anticancer mechanisms by IL-6, 5 (S)-HETE And ROS generation in pancreatic human

Abstract

Pancreatic carcinogenesis is characterized by the activationof inflammatory signaling pathways. Numerous studies havedemonstrated the role of essential fatty acids (EFAs) in pancreaticcancer initiation and progression, but the underlying molecularmechanisms have not been completely elucidated. Here, we studiedthe effects of two omega-3 EFAs, the eicosapentaenoic acid (EPA)and docosahexaenoic acid (DHA) and the omega-6 fatty acid, thearachidonic acid (AA) on a human pancreatic cell line (PANC-1).We determined the release of interleukin-6 (IL-6) as inflammatorymarker in supernatants from PANC-1 cultures using ELISA, as wellas their gene expression by qRT-PCR. Cell viability (Rezasurin) andreactive oxygen species (ROS) production (DCFH-DA assay kit)by fluorimetry. Eicosanoids generation and lipid cell profile by Highpressure liquid and Gas chromatography (HPLC and GC).We observeda significant reduction in cell viability in DHA and EPA comparedto AA and control (ethanol) treatments (P<0.05). Moreover,we demonstrated an increased apoptotic levels in DHA and EPAtreated cells in comparison with the control and AA treatment, probablymediated by ROS production (P <0.05). A diminution of IL-6 geneexpression (P< 0.01) and liberation (p< 0.02) resulted after DHA andEPA treated cells. The release of proinflammatory eicosanoids: 13-HODE and 5(S)-HETE decreased on EPA and DHA treated cellscompared with AA and control (p<0.05).Therefore, we demonstratedthat omega-3 EFAs may reduce the growth of PANC-1 by severalmechanisms that include significant increase of ROS production,diminution of lipid peroxides and down regulation of gene expressionand secretion of inflammatory cytokines such as IL-6.Keywords: pancreatic cancer, essential fatty acids, eicosanoids.