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Abstract Title:

Regulation of the oxidative balance with coenzyme Q10 sensitizes human glioblastoma cells to radiation and temozolomide.

Abstract Source:

Radiother Oncol. 2018 May 18. Epub 2018 May 18. PMID: 29784452

Abstract Author(s):

Javier Frontiñán-Rubio, Raquel María Santiago-Mora, Consuelo María Nieva-Velasco, Gustavo Ferrín, Alicia Martínez-González, María Victoria Gómez, María Moreno, Julia Ariza, Eva Lozano, Jacinto Arjona-Gutiérrez, Antonio Gil-Agudo, Manuel De la Mata, Milica Pesic, Juan Ramón Peinado, José M Villalba, Luis Pérez-Romasanta, Víctor M Pérez-García, Francisco J Alcaín, Mario Durán-Prado

Article Affiliation:

Javier Frontiñán-Rubio

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 (O) and HOwere 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 ofγH2AX (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 Oand HOwhile 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.

Study Type : In Vitro Study

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Sayer Ji
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