title: Combination of unsaturated fatty acids and ionizing radiation on human glioma cells: cellular, biochemical and gene expression analysis.
abstract: BACKGROUND
  Based on previous observations a potential resort in the therapy of the particularly radioresistant glioma would be its treatment with unsaturated fatty acids (UFAs) combined with irradiation.
  
  
  METHODS
  We evaluated the effect of different UFAs (arachidonic acid (AA), docosahexaenoic acid (DHA), gamma-linolenic acid (GLA), eicosapentaenoic acid (EPA) and oleic acid (OA)) on human U87 MG glioma cell line by classical biochemical end-point assays, impedance-based, real-time cellular and holographic microscopic analysis. We further analyzed AA, DHA, and GLA at morphological, gene and miRNA expression level.
  
  
  RESULTS
  Corresponding to LDH-, MTS assays and real-time cytoxicity profiles AA, DHA, and GLA enhanced the radio sensitivity of glioma cells. The collective application of polyunsaturated fatty acids (PUFAs) and irradiation significantly changed the expression of EGR1, TNF-α, NOTCH1, c-MYC, TP53, HMOX1, AKR1C1, NQO1, while up-regulation of GADD45A, EGR1, GRP78, DDIT3, c-MYC, FOSL1 were recorded both in response to PUFA treatment or irradiation alone. Among the analyzed miRNAs miR-146 and miR-181a were induced by DHA treatment. Overexpression of miR-146 was also detected by combined treatment of GLA and irradiation.
  
  
  CONCLUSIONS
  Because PUFAs increased the radio responsiveness of glioma cells as assessed by biochemical and cellular assays, they might increase the therapeutic efficacy of radiation in treatment of gliomas. We demonstrated that treatment with DHA, AA and GLA as adjunct to irradiation up-regulated the expression of oxidative-stress and endoplasmic reticulum stress related genes, and affected NOTCH1 expression, which could explain their additive effects.
authors.forename: Otilia
authors.initials: O
authors.lastname: Antal
authors.forename: László
authors.initials: L
authors.lastname: Hackler
authors.forename: Junhui
authors.initials: J
authors.lastname: Shen
authors.forename: Imola
authors.initials: I
authors.lastname: Mán
authors.forename: Katalin
authors.initials: K
authors.lastname: Hideghéty
authors.forename: Klára
authors.initials: K
authors.lastname: Kitajka
authors.affiliation: Laboratory for Functional Genomics, Institute of Genetics, Biological Research Center of the Hungarian Academy of Sciences, Szeged H-6726, Hungary. puskas.szbk@gmail.com.
authors.forename: László G
authors.initials: LG
authors.lastname: Puskás
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D048430:Cell Shape / Q000187:drug effects / Q000528:radiation effects; D004354:Drug Screening Assays, Antitumor; D000091342:Endoplasmic Reticulum Chaperone BiP; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000528:radiation effects; D005910:Glioma; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D059467:Transcriptome / Q000187:drug effects / Q000528:radiation effects
chemical_list: D000970:Antineoplastic Agents; D000091342:Endoplasmic Reticulum Chaperone BiP; D005231:Fatty Acids, Unsaturated; C000717247:HSPA5 protein, human; D035683:MicroRNAs; D007770:L-Lactate Dehydrogenase