Regulation of the oxidative balance with coenzyme Q10 sensitizes human glioblastoma cells to radiation and temozolomide.
2018
Autori:
Frontiñán-Rubio, JavierSantiago-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
Pešić, Milica
Peinado, Juan Ramón
Villalba, José M.
Pérez-Romasanta, Luis
Pérez-García, Víctor M.
Alcaín, Francisco J.
Durán-Prado, Mario
Tip dokumenta:
Članak u časopisu (Recenzirana verzija)
,
© 2018 Elsevier B.V.
Metapodaci
Prikaz svih podataka o dokumentuApstrakt:
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 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. RESULTS 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. 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.
Ključne reči:
Antioxidant capacity; Apoptosis; Glycolytic metabolism; Ionizing radiation; Reactive oxygen species; UbiquinoneIzvor:
Radiotherapy and Oncology, 2018
DOI: 10.1016/j.radonc.2018.04.033
PubMed: 29784452
WoS: 000440972900009
Scopus: 2-s2.0-85047075724
URI
https://www.sciencedirect.com/science/article/pii/S0167814018302408?via%3Dihubhttps://radar.ibiss.bg.ac.rs/handle/123456789/3070