title: Lipid alterations in human colon epithelial cells induced to differentiation and/or apoptosis by butyrate and polyunsaturated fatty acids.
abstract: The present study highlights the important association between lipid alterations and differentiation/apoptotic responses in human colon differentiating (FHC) and nondifferentiating (HCT-116) cell lines after their treatment with short-chain fatty acid sodium butyrate (NaBt), polyunsaturated fatty acids (PUFAs), and/or their combination. Our data from GC/MS and LC/MS/MS showed an effective incorporation and metabolization of the supplemented arachidonic acid (AA) or docosahexaenoic acid (DHA), resulting in an enhanced content of the respective PUFA in individual phospholipid (PL) classes and an altered composition of the whole cellular fatty acid spectrum in both FHC and HCT-116 cells. We provide novel evidence that NaBt combined with PUFAs additionally modulated AA and DHA cellular levels and caused their shift from triacylglycerol to PL fractions. NaBt increased, while AA, DHA and their combination with NaBt decreased endogenous fatty acid synthesis in FHC but not in HCT-116 cells. Fatty acid treatment also altered membrane lipid structure, augmented cytoplasmic lipid droplet accumulation, reactive oxygen species (ROS) production and dissipation of the mitochondrial membrane potential. All these parameters were significantly enhanced by combined NaBt/PUFA treatment, but only in FHC cells was this accompanied by highly increased apoptosis and suppressed differentiation. Moreover, the most significant changes of ROS production, differentiation and apoptosis among the parameters studied, the highest effects of combined NaBt/PUFA treatment and a lower sensitivity of HCT-116 cells were confirmed using two-way ANOVA. Our results demonstrate an important role of fatty acid-induced lipid alterations in the different apoptotic/differentiation response of colon cells with various carcinogenic potential.
authors.affiliation: Department of Cytokinetics, Institute of Biophysics, Academy of Sciences of the Czech Republic, vvi, Brno, Czech Republic.
authors.forename: Jiřina
authors.initials: J
authors.lastname: Hofmanová
authors.forename: Miroslav
authors.initials: M
authors.lastname: Ciganek
authors.forename: Josef
authors.initials: J
authors.lastname: Slavík
authors.forename: Alois
authors.initials: A
authors.lastname: Kozubík
authors.forename: Lenka
authors.initials: L
authors.lastname: Stixová
authors.forename: Alena
authors.initials: A
authors.lastname: Vaculová
authors.forename: Ladislav
authors.initials: L
authors.lastname: Dušek
authors.forename: Miroslav
authors.initials: M
authors.lastname: Machala
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D016718:Arachidonic Acid / Q000494:pharmacology*; D002087:Butyrates / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects*; D002853:Chromatography, Liquid; D003106:Colon / Q000166:cytology; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D045325:HCT116 Cells; D006801:Humans; D010743:Phospholipids / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D053719:Tandem Mass Spectrometry; D014280:Triglycerides / Q000378:metabolism
chemical_list: D002087:Butyrates; D010743:Phospholipids; D017382:Reactive Oxygen Species; D014280:Triglycerides; D004281:Docosahexaenoic Acids; D016718:Arachidonic Acid