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

Otilia Antal, Mária Péter, László Hackler, Imola Mán, Gábor Szebeni, Ferhan Ayaydin, Katalin Hideghéty, László Vigh, Klára Kitajka, Gábor Balogh, Laszló G. Puskás

Research output: Contribution to journalArticle

12 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1271-1282
Number of pages12
JournalBiochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
Volume1851
Issue number9
DOIs
Publication statusPublished - Jul 4 2015

Keywords

  • Gamma-linolenic acid
  • Gene expression
  • Glioma
  • Irradiation
  • Lipid droplet
  • Lipidomic analysis

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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