In addition to various roles in membrane structure and metabolism, polyunsaturated fatty acids have effects on signal transduction and on the regulation of gene expression. Eicosapentaenoic acid (EPA) is an ω-3 fatty acid which is known to induce cell cycle arrest and apoptosis in pancreatic tumour cells. NFκB is a key transcription factor regulating genes involved in the immune response and has been implicated in apoptotic pathways. In this study we investigated the effect of eicosapentanoic acid on the NFκB pathway in pancreatic tumour cells. The pancreatic cell line MIA PaCa2 was incubated in the presence of the fatty acids EPA (n-3), arachidonic acid (AA, n-6) or oleic acid (OA, n-9) before pulsing with TNF to provide a kinetic assessment of NFκB activation and IκBα degradation. Pre-incubation of pancreatic cells with EPA or AA for 2 h before pulsing with TNF preserved IκBα but did not prevent NFκB activation. Indeed, NFκB activation was prolonged after exposure to EPA. N-acetyl-L-cysteine did not influence the effect of EPA on TNF-stimulated IκBα degradation. These results suggest that the ω-3 fatty acid EPA perturbs the NFκB pathway by a novel mechanism. This mechanism may be important in delineating alternative pathways to NFκB activation.

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