Regulation of the oxidative balance with coenzyme Q10 sensitizes human glioblastoma cells to radiation and temozolomide. Issue 2 (August 2018)

• Record Type: Journal Article
• Authors: Frontiñán-Rubio, Javier; Santiago-Mora, Raquel María; Nieva-Velasco, Consuelo María; Ferrín, Gustavo; Martínez-González, Alicia; Gómez, María Victoria; Moreno, María; Ariza, Julia; Lozano, Eva; Arjona-Gutiérrez, Jacinto; Gil-Agudo, Antonio; De la Mata, Manuel; Pesic, Milica; Peinado, Juan Ramón; Villalba, José M.; Pérez-Romasanta, Luis; Pérez-García, Víctor M.; Alcaín, Francisco J.; Durán-Prado, Mario
• Is Part Of: Radiotherapy and oncology. Volume 128:Issue 2(2018)
• Page Start: 236
• Page End: 244
• Publication Date: 2018-08
• Subjects: Antioxidant capacity -- Apoptosis -- Glycolytic metabolism -- Ionizing radiation -- Reactive oxygen species -- Ubiquinone; Oncology -- Periodicals; Radiotherapy -- Periodicals; Tumors -- Periodicals; Medical Oncology -- Periodicals; Neoplasms -- radiotherapy -- Periodicals; Radiotherapy -- Periodicals; Radiothérapie -- Périodiques; Cancérologie -- Périodiques; Tumeurs -- Périodiques; Electronic journals; 616.9940642
• DOI: 10.1016/j.radonc.2018.04.033
• Languages: English
• ISSNs: 0167-8140

Abstract

Abstract: Objectives: To investigate how the modulation of the oxidative balance affects cytotoxic therapies in glioblastoma, in vitro . Material and methods: Human glioblastoma U251 and T98 cells and normal astrocytes C8D1A were loaded with coenzyme Q10 (CoQ). Mitochondrial superoxide ion (O2 − ) and H2 O2 were measured by fluorescence microscopy. OXPHOS performance was assessed in U251 cells with an oxytherm Clark-type electrode. Radio- and chemotherapy cytotoxicity was assessed by immunostaining of γH2AX (24 h), annexin V and nuclei morphology, at short (72 h) and long (15 d) time. Hif-1α, SOD1, SOD2 and NQO1 were determined by immunolabeling. Catalase activity was measured by classic enzymatic assay. Glutathione levels and total antioxidant capacity were quantified using commercial kits. Results: CoQ did not affect oxygen consumption but reduced the level of O2 − and H2 O2 while shifted to a pro-oxidant cell status mainly due to a decrease in catalase activity and SOD2 level. Hif-1α was dampened, echoed by a decrease lactate and several key metabolites involved in glutathione synthesis. CoQ-treated cells were twofold more sensitive than control to radiation-induced DNA damage and apoptosis in short and long-term clonogenic assays, potentiating TMZ-induced cytotoxicity, without affecting non-transformed astrocytes. Conclusions: CoQ acts as sensitizer for cytotoxic therapies, disarming GBM cells, but not normal astrocytes, against further pro-oxidant injuries, being potentially useful in clinical practice for this fatal pathology.