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Regulation of the oxidative balance with coenzyme Q10 sensitizes human glioblastoma cells to radiation and temozolomide.
dc.creator | Frontiñán-Rubio, Javier | |
dc.creator | Santiago-Mora, Raquel María | |
dc.creator | Nieva-Velasco, Consuelo María | |
dc.creator | Ferrín, Gustavo | |
dc.creator | Martínez-González, Alicia | |
dc.creator | Gómez, María Victoria | |
dc.creator | Moreno, María | |
dc.creator | Ariza, Julia | |
dc.creator | Lozano, Eva | |
dc.creator | Arjona-Gutiérrez, Jacinto | |
dc.creator | Gil-Agudo, Antonio | |
dc.creator | De la Mata, Manuel | |
dc.creator | Pešić, Milica | |
dc.creator | Peinado, Juan Ramón | |
dc.creator | Villalba, José M. | |
dc.creator | Pérez-Romasanta, Luis | |
dc.creator | Pérez-García, Víctor M. | |
dc.creator | Alcaín, Francisco J. | |
dc.creator | Durán-Prado, Mario | |
dc.date | 2019-05-18 | |
dc.date.accessioned | 2018-05-31T09:35:13Z | |
dc.date.available | 2019-05-18 | |
dc.date.issued | 2018 | |
dc.identifier.uri | https://www.sciencedirect.com/science/article/pii/S0167814018302408?via%3Dihub | |
dc.identifier.uri | https://radar.ibiss.bg.ac.rs/handle/123456789/3070 | |
dc.description.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 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. | en |
dc.rights | embargoedAccess | |
dc.source | Radiotherapy and Oncology | |
dc.subject | Antioxidant capacity | |
dc.subject | Apoptosis | |
dc.subject | Glycolytic metabolism | |
dc.subject | Ionizing radiation | |
dc.subject | Reactive oxygen species | |
dc.subject | Ubiquinone | |
dc.title | Regulation of the oxidative balance with coenzyme Q10 sensitizes human glioblastoma cells to radiation and temozolomide. | en |
dc.type | article | en |
dc.rights.license | ARR | |
dcterms.abstract | Aлцаíн, Францисцо Ј.; Дурáн-Прадо, Марио; Фронтиñáн-Рубио, Јавиер; Сантиаго-Мора, Раqуел Марíа; Ниева-Веласцо, Цонсуело Марíа; Феррíн, Густаво; Мартíнез-Гонзáлез, Aлициа; Гóмез, Марíа Вицториа; Морено, Марíа; Aриза, Јулиа; Лозано, Ева; Aрјона-Гутиéррез, Јацинто; Гил-Aгудо, Aнтонио; Де ла Мата, Мануел; Пеинадо, Јуан Рамóн; Виллалба, Јосé М.; Пéрез-Ромасанта, Луис; Пéрез-Гарцíа, Вíцтор М.; Пешић, Милица; | |
dc.rights.holder | © 2018 Elsevier B.V. | |
dc.identifier.doi | 10.1016/j.radonc.2018.04.033 | |
dc.identifier.pmid | 29784452 | |
dc.identifier.scopus | 2-s2.0-85047075724 | |
dc.identifier.wos | 000440972900009 | |
dc.citation.apa | Frontiñán-Rubio, J., Santiago-Mora, R. M., Nieva-Velasco, C. M., Ferrín, G., Martínez-González, A., Gómez, M. V., … Durán-Prado, M. (2018). Regulation of the oxidative balance with coenzyme Q10 sensitizes human glioblastoma cells to radiation and temozolomide. Radiotherapy and Oncology, DOI:10.1016/j.radonc.2018.04.033. | |
dc.citation.vancouver | Frontiñán-Rubio J, Santiago-Mora RM, Nieva-Velasco CM, Ferrín G, Martínez-González A, Gómez MV, Moreno M, Ariza J, Lozano E, Arjona-Gutiérrez J, Gil-Agudo A, De la Mata M, Pesic M, Peinado JR, Villalba JM, Pérez-Romasanta L, Pérez-García VM, Alcaín FJ, Durán-Prado M. Regulation of the oxidative balance with coenzyme Q10 sensitizes human glioblastoma cells to radiation and temozolomide. Radiother Oncol. 2018;DOI:10.1016/j.radonc.2018.04.033 | |
dc.type.version | acceptedVersion | |
dc.identifier.fulltext | https://radar.ibiss.bg.ac.rs/bitstream/id/4298/RadiotherOncol_2018.pdf | |
dc.citation.rank | M21 |