Eicosapentaenoic acid perturbs signalling via the NFkappaB transcriptional pathway in pancreatic tumour cells.
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 omega-3 fatty acid which is known to induce cell cycle arrest and apoptosis in pancreatic tumour cells. NFkappaB 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 NFkappaB 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 NFkappaB activation and IkappaBalpha degradation. Pre-incubation of pancreatic cells with EPA or AA for 2 h before pulsing with TNF preserved IkappaBalpha but did not prevent NFkappaB activation. Indeed, NFkappaB activation was prolonged after exposure to EPA. N-acetyl-L-cysteine did not influence the effect of EPA on TNF-stimulated IkappaBalpha degradation. These results suggest that the omega-3 fatty acid EPA perturbs the NFkappaB pathway by a novel mechanism. This mechanism may be important in delineating alternative pathways to NFkappaB activation.
Ross
James A
JA
Tissue Injury and Repair Group, Centre for Inflammation Research, University of Edinburgh Department of Clinical and Surgical Sciences, Medical School, Teviot Place, Edinburgh EH8 9AG, UK. j.a.ross@ed.ac.uk
Maingay
Jean P
JP
Fearon
Kenneth C H
KC
Sangster
Kathryn
K
Powell
James J
JJ
D000111:Acetylcysteine / Q000494:pharmacology; D021581:Active Transport, Cell Nucleus; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis; D015153:Blotting, Western; D045744:Cell Line, Tumor; D003593:Cytoplasm / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D003720:Densitometry; D015118:Eicosapentaenoic Acid / Q000494:pharmacology*; D015525:Fatty Acids, Omega-3 / Q000378:metabolism; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000378:metabolism*; D015398:Signal Transduction; D013997:Time Factors; D014158:Transcription, Genetic
D000975:Antioxidants; D015525:Fatty Acids, Omega-3; D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D000072000:NF-KappaB Inhibitor alpha; D004247:DNA; D015118:Eicosapentaenoic Acid; D000111:Acetylcysteine