title: Lipidomic analysis reveals a radiosensitizing role of gamma-linolenic acid in glioma cells.
abstract: Previous studies have demonstrated that gamma-linolenic acid (GLA) is effective against glioma cells under both in vitro and in vivo conditions. In the present study we determined how GLA alone or in combination with irradiation alters the fatty acid (FA) and lipid profiles, the lipid droplet (LD) content, the lipid biosynthetic gene expression and the apoptosis of glioma cells. In GLA-treated cells direct correlations were found between the levels of various FAs and the expression of the corresponding FA biosynthetic genes. The total levels of saturated and monosaturated FAs decreased in concert with the down-regulation of FASN and SCD1 gene expression. Similarly, decreased FADS1 gene expression was paralleled by lowered arachidonic acid (20:4 n-6) and eicosapentaenoic acid (20:5 n-3) contents, while the down-regulation of FADS2 expression was accompanied by a diminished docosahexaenoic acid (22:6 n-3) content. Detailed mass spectrometric analyses revealed that individual treatments gave rise to distinct lipidomic fingerprints. Following uptake, GLA was subjected to elongation, resulting in dihomo-gamma-linolenic acid (20:3 n-6, DGLA), which was used for the synthesis of the LD constituent triacylglycerols and cholesteryl esters. Accordingly, an increased number of LDs were observed in response to GLA administration after irradiation. GLA increased the radioresponsiveness of U87 MG cells, as demonstrated by an increase in the number of apoptotic cells determined by FACS analysis. In conclusion, treatment with GLA increased the apoptosis of irradiated glioma cells, and GLA might therefore increase the therapeutic efficacy of irradiation in the treatment of gliomas.
authors.affiliation: Laboratory for Functional Genomics, Institute of Genetics, Biological Research Center of the Hungarian Academy of Sciences, Szeged H-6726, Hungary.
authors.forename: Otilia
authors.initials: O
authors.lastname: Antal
authors.affiliation: Laboratory of Molecular Stress Biology, Membrane and Stress Biology Unit, Institute of Biochemistry, Biological Research Center of the Hungarian Academy of Sciences, Szeged H-6726, Hungary.
authors.forename: Mária
authors.initials: M
authors.lastname: Péter
authors.affiliation: Avidin Ltd., Szeged H-6726, Hungary(3).
authors.forename: László
authors.initials: L
authors.lastname: Hackler
authors.affiliation: Avidin Ltd., Szeged H-6726, Hungary(3).
authors.forename: Imola
authors.initials: I
authors.lastname: Mán
authors.affiliation: Avidin Ltd., Szeged H-6726, Hungary(3).
authors.forename: Gábor
authors.initials: G
authors.lastname: Szebeni
authors.affiliation: Cellular Imaging Laboratory, Biological Research Center of the Hungarian Academy of Sciences, Szeged H-6726, Hungary.
authors.forename: Ferhan
authors.initials: F
authors.lastname: Ayaydin
authors.affiliation: Department of Oncotherapy, Faculty of Medicine, University of Szeged, H-6720, Hungary.
authors.forename: Katalin
authors.initials: K
authors.lastname: Hideghéty
authors.affiliation: Laboratory of Molecular Stress Biology, Membrane and Stress Biology Unit, Institute of Biochemistry, Biological Research Center of the Hungarian Academy of Sciences, Szeged H-6726, Hungary.
authors.forename: László
authors.initials: L
authors.lastname: Vigh
authors.affiliation: Laboratory for Functional Genomics, Institute of Genetics, Biological Research Center of the Hungarian Academy of Sciences, Szeged H-6726, Hungary; Avidin Ltd., Szeged H-6726, Hungary(3).
authors.forename: Klára
authors.initials: K
authors.lastname: Kitajka
authors.affiliation: Laboratory of Molecular Stress Biology, Membrane and Stress Biology Unit, Institute of Biochemistry, Biological Research Center of the Hungarian Academy of Sciences, Szeged H-6726, Hungary.
authors.forename: Gábor
authors.initials: G
authors.lastname: Balogh
authors.affiliation: Laboratory for Functional Genomics, Institute of Genetics, Biological Research Center of the Hungarian Academy of Sciences, Szeged H-6726, Hungary; Avidin Ltd., Szeged H-6726, Hungary(3). Electronic address: puskas.szbk@gmail.com.
authors.forename: Laszló G
authors.initials: LG
authors.lastname: Puskás
mesh_terms: D015126:8,11,14-Eicosatrienoic Acid / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D016718:Arachidonic Acid / Q000378:metabolism; D045744:Cell Line, Tumor; D002788:Cholesterol Esters / Q000378:metabolism; D000090943:Delta-5 Fatty Acid Desaturase; D004281:Docosahexaenoic Acids / Q000378:metabolism; D015118:Eicosapentaenoic Acid / Q000378:metabolism; D044943:Fatty Acid Desaturases / Q000235:genetics / Q000378:metabolism; D054890:Fatty Acid Synthase, Type I / Q000235:genetics / Q000378:metabolism; D005720:Gamma Rays; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D066292:Lipid Droplets / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects; D050356:Lipid Metabolism / Q000187:drug effects* / Q000528:radiation effects; D009457:Neuroglia / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects; D011838:Radiation-Sensitizing Agents / Q000378:metabolism / Q000494:pharmacology*; D013230:Stearoyl-CoA Desaturase / Q000235:genetics / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism; D017965:gamma-Linolenic Acid / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D002788:Cholesterol Esters; D000090943:Delta-5 Fatty Acid Desaturase; D011838:Radiation-Sensitizing Agents; D014280:Triglycerides; D004281:Docosahexaenoic Acids; D016718:Arachidonic Acid; D017965:gamma-Linolenic Acid; D015118:Eicosapentaenoic Acid; D044943:Fatty Acid Desaturases; C523776:SCD1 protein, human; D013230:Stearoyl-CoA Desaturase; C000716847:FADS1 protein, human; C533241:FADS2 protein, human; C518729:FASN protein, human; D054890:Fatty Acid Synthase, Type I; D015126:8,11,14-Eicosatrienoic Acid
keywords: Gamma-linolenic acid; Gene expression; Glioma; Irradiation; Lipid droplet; Lipidomic analysis