RT Journal Article
T1 Regulation of the oxidative balance with coenzyme Q10 sensitizes human glioblastoma cells to radiation and temozolomide.
A1 Frontiñan-Rubio, Javier
A1 Santiago-Mora, Raquel Maria
A1 Nieva-Velasco, Consuelo Maria
A1 Ferrin, Gustavo
A1 Martinez-Gonzalez, Alicia
A1 Gomez, Maria Victoria
A1 Moreno, Maria
A1 Ariza, Julia
A1 Lozano, Eva
A1 Arjona-Gutierrez, Jacinto
A1 Gil-Agudo, Antonio
A1 De la Mata, Manuel
A1 Pesic, Milica
A1 Peinado, Juan Ramon
A1 Villalba, Jose M
A1 Perez-Romasanta, Luis
A1 Perez-Garcia, Victor M
A1 Alcain, Francisco J
A1 Duran-Prado, Mario
K1 Antioxidant capacity
K1 Apoptosis
K1 Glycolytic metabolism
K1 Ionizing radiation
K1 Reactive oxygen species
K1 Ubiquinone
AB To investigate how the modulation of the oxidative balance affects cytotoxic therapies in glioblastoma, in vitro. Human glioblastoma U251 and T98 cells and normal astrocytes C8D1A were loaded with coenzyme Q10 (CoQ). Mitochondrial superoxide ion (O2-) and H2O2 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. CoQ did not affect oxygen consumption but reduced the level of O2- and H2O2 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. 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.
PB Elsevier
YR 2018
FD 2018-04-29
LK http://hdl.handle.net/10668/12492
UL http://hdl.handle.net/10668/12492
LA en
NO Frontiñán-Rubio J, Santiago-Mora RM, Nieva-Velasco CM, Ferrín G, Martínez-González A, Gómez MV, et al. Regulation of the oxidative balance with coenzyme Q10 sensitizes human glioblastoma cells to radiation and temozolomide. Radiother Oncol. 2018 Aug;128(2):236-244
NO Especies reactivas de oxígeno
DS RISalud
RD Apr 7, 2025