title: Toxic effects of n-3 polyunsaturated fatty acids in human lung A549 cells.
abstract: N-3 polyunsaturated fatty acids (PUFAs), particularly eicosapentaenoic acid (EPA, 20:5) and docosahexaenoic acid (DHA, 22:6) are crucial for the prevention of lung cancer. PUFAs may act through alteration of membrane fluidity and cell surface receptor functions; modulation of cyclooxygenase activity; and increased cellular oxidative stress, which may induce apoptosis and autophagy. Therefore the aim of the study was to investigate whether EPA and DHA (25-100 μM) are able to reduce human lung cancer cell growth through oxidative stress influence on autophagy and apoptosis. It was found that both EPA and DHA in the concentration-dependent manner suppressed the cell viability, enhanced cell death, induced activation of caspase-3/7 and potentiated intracellular oxidative DNA and protein damage. In response to PUFAs intracellular autophagic vacuolization occurred and the observed effect was reverted when the autophagy inhibitor 3-methyladenine (3-MA) was applied. The inhibition of the autophagic process enhanced the cell viability, suppressed cell death, and decreased activation of caspase-3/7 indicating that EPA and DHA-induced autophagy amplified A549 apoptotic cell death.
authors.affiliation: Medical University of Silesia, School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec, Department of Biopharmacy, Sosnowiec, Poland. Electronic address: azajdel@sum.edu.pl.
authors.forename: Alicja
authors.initials: A
authors.lastname: Zajdel
authors.affiliation: Medical University of Silesia, School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec, Department of Biopharmacy, Sosnowiec, Poland.
authors.forename: Adam
authors.initials: A
authors.lastname: Wilczok
authors.affiliation: Medical University of Silesia, School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec, Department of Biopharmacy, Sosnowiec, Poland.
authors.forename: Michał
authors.initials: M
authors.lastname: Tarkowski
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004281:Docosahexaenoic Acids / Q000633:toxicity; D015118:Eicosapentaenoic Acid / Q000633:toxicity; D015525:Fatty Acids, Omega-3 / Q000633:toxicity*; D006801:Humans; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D015525:Fatty Acids, Omega-3; D017382:Reactive Oxygen Species; D004281:Docosahexaenoic Acids; D015118:Eicosapentaenoic Acid
keywords: A549 lung cancer cells; Apoptosis; Autophagy; Docosahexaenoic acid; Eicosapentaenoic acid; Oxidative damage