Combination of unsaturated fatty acids and ionizing radiation on human glioma cells

Cellular, biochemical and gene expression analysis

Otilia Antal, László Hackler, Junhui Shen, Imola Mán, K. Hideghéty, K. Kitajka, L. Puskás

Research output: Contribution to journalArticle

26 Citations (Scopus)

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.

Original languageEnglish
Article number142
JournalLipids in Health and Disease
Volume13
Issue number1
DOIs
Publication statusPublished - Sep 2 2014

Fingerprint

gamma-Linolenic Acid
Docosahexaenoic Acids
Ionizing radiation
Ionizing Radiation
Unsaturated Fatty Acids
Gene expression
Glioma
Arachidonic Acid
Irradiation
Gene Expression
Assays
MicroRNAs
Radio
Genes
Endpoint Determination
Endoplasmic Reticulum Stress
Oxidative stress
Eicosapentaenoic Acid
Oleic Acid
Electric Impedance

Keywords

  • Gene expression
  • Glioma
  • Irradiation
  • miRNA expression
  • Polyunsaturated fatty acids (PUFAs)

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Biochemistry, medical
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology
  • Medicine(all)

Cite this

Combination of unsaturated fatty acids and ionizing radiation on human glioma cells : Cellular, biochemical and gene expression analysis. / Antal, Otilia; Hackler, László; Shen, Junhui; Mán, Imola; Hideghéty, K.; Kitajka, K.; Puskás, L.

In: Lipids in Health and Disease, Vol. 13, No. 1, 142, 02.09.2014.

Research output: Contribution to journalArticle

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T2 - Cellular, biochemical and gene expression analysis

AU - Antal, Otilia

AU - Hackler, László

AU - Shen, Junhui

AU - Mán, Imola

AU - Hideghéty, K.

AU - Kitajka, K.

AU - Puskás, L.

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AB - 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.

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