Lipidomic analysis reveals a radiosensitizing role of gamma-linolenic acid in glioma cells

• Published in: Biochimica et biophysica acta Vol. 1851; no. 9; pp. 1271 - 1282
• Main Authors: Antal, Otilia, Péter, Mária, Hackler, László, Mán, Imola, Szebeni, Gábor, Ayaydin, Ferhan, Hideghéty, Katalin, Vigh, László, Kitajka, Klára, Balogh, Gábor, Puskás, Laszló G
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.09.2015
• Subjects: 8,11,14-Eicosatrienoic Acid - metabolism; Apoptosis - drug effects; Apoptosis - radiation effects; Arachidonic Acid - metabolism; Cell Line, Tumor; Cholesterol Esters - metabolism; Docosahexaenoic Acids - metabolism; Eicosapentaenoic Acid - metabolism; Fatty Acid Desaturases - genetics; Fatty Acid Desaturases - metabolism; Fatty Acid Synthase, Type I - genetics; Fatty Acid Synthase, Type I - metabolism; Gamma Rays; Gamma-linolenic acid; gamma-Linolenic Acid - metabolism; gamma-Linolenic Acid - pharmacology; Gene expression; Gene Expression Regulation, Neoplastic; Glioma; Humans; Irradiation; Lipid droplet; Lipid Droplets - chemistry; Lipid Droplets - drug effects; Lipid Droplets - metabolism; Lipid Droplets - radiation effects; Lipid Metabolism - drug effects; Lipid Metabolism - radiation effects; Lipidomic analysis; Neuroglia - drug effects; Neuroglia - metabolism; Neuroglia - pathology; Neuroglia - radiation effects; Radiation-Sensitizing Agents - metabolism; Radiation-Sensitizing Agents - pharmacology; Stearoyl-CoA Desaturase - genetics; Stearoyl-CoA Desaturase - metabolism; Triglycerides - metabolism; Irradiation; Gamma-linolenic acid; Lipid droplet; Glioma; Lipidomic analysis; Gene expression
• ISSN: 1388-1981; 0006-3002; 1879-2618
• DOI: 10.1016/j.bbalip.2015.06.003

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. •GLA increases the radioresponsiveness of U87 MG cells.•FA levels and FA biosynthetic gene expression correlated following GLA-treatment.•GLA incorporates into both membrane and storage lipids.•Increased PUFA content contributes to PS oxidation-mediated apoptosis.•GLA treatment alone or in combination with irradiation reshapes the whole lipidome.