Abstract
Glioblastoma multiforme is the most frequent and aggressive primary brain tumor. A strong rationale to identify innovative approaches to treat these tumors is required since treatment failures result in local recurrences and median survivals range from 9 to 12 months. Glioma cells are reported to have less mitochondrial content compared to adjacent normal brain cells. Based on this difference, we suggest a new strategy, utilizing protection of normal brain cells by mitochondria-targeted electron scavengers and antioxidants-nitroxides-thus allowing for the escalation of the radiation doses. In this paper, we report that a conjugate of nitroxide with a hydrophobic cation, triphenyl-phosphonium (TPEY-Tempo), significantly protected brain endothelial cells from γ-irradiation-induced apoptosis while radiosensitizing brain tumor cells. Thus, TPEY-Tempo may be a promising adjunct in the treatment of glioblastoma with the potential to not only prolong survival but also to maintain quality of life and reduce treatment toxicity.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Apoptosis / drug effects*
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Apoptosis / radiation effects
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Brain / cytology*
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Brain Neoplasms / pathology
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Brain Neoplasms / ultrastructure
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Caspase 3 / metabolism
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Cell Line, Transformed
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Cyclic N-Oxides / metabolism
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Cytochromes c / metabolism
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Dose-Response Relationship, Radiation
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Electron Transport Complex IV / metabolism
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Endothelial Cells / drug effects
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Endothelial Cells / radiation effects
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Endothelial Cells / ultrastructure
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Gamma Rays / adverse effects
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Glioma / pathology
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Glioma / ultrastructure
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Humans
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Mitochondria / metabolism
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Mitochondria / radiation effects*
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Neuroprotective Agents / pharmacology*
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Nitrogen Oxides / chemistry*
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Organic Chemicals / metabolism
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Organoselenium Compounds / pharmacology*
Substances
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Cyclic N-Oxides
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MitoTracker Red 580
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Neuroprotective Agents
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Nitrogen Oxides
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Organic Chemicals
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Organoselenium Compounds
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triphenylselenonium chloride
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Cytochromes c
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Electron Transport Complex IV
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Caspase 3
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TEMPO