Combination of unsaturated fatty acids and ionizing radiation on human glioma cells: cellular, biochemical and gene expression analysis
1 Laboratory for Functional Genomics, Institute of Genetics, Biological Research Center of the Hungarian Academy of Sciences, Szeged H-6726, Hungary
2 Avidin Ltd., Szeged H-6726, Hungary
3 Tongji University School of Medicine, Shanghai 200092, China
4 Department of Oncotherapy, Faculty of Medicine, University of Szeged, Szeged H-6720, Hungary
Lipids in Health and Disease 2014, 13:142 doi:10.1186/1476-511X-13-142Published: 2 September 2014
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.
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.
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.
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.