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Protection of normal brain cells from gamma-irradiation-induced apoptosis by a mitochondria-targeted triphenyl-phosphonium-nitroxide: a possible utility in glioblastoma therapy.

Authors
Huang-Z; Jiang-J; Belikova-NA; Stoyanovsky-DA; Kagan-VE; Mintz-AH
Source
J Neuro-Oncol 2010 Oct; 100(1):1-8
NIOSHTIC No.
20037966
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 gamma-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.
Keywords
Cancer; Brain-tumors; Blastogenesis; Tumors; Survival-rate; Cellular-structures; Medical-treatment; Oncogenic-agents; Chemotherapy; Radiation-therapy; Radiobiology; Cell-alteration; Antioxidants; Nitrogen-oxides; Hydrophobic-bonds; Irradiation; Author Keywords: Glioblastoma; Mitochondria; Triphenyl-phosphonium conjugated nitroxide; gamma-irradiation; Apoptosis
Contact
Arlan H. Mintz, Department of Neurosurgery, University of Pittsburgh, Cancer Pavillion, Shadyside Hospital, 5150 Center Avenue, Suite 430, Pittsburgh, PA 15232, USA
CODEN
JNODD2
Publication Date
20101001
Document Type
Journal Article
Email Address
mintzah@upmc.edu
Funding Type
Grant
Fiscal Year
2011
NTIS Accession No.
NTIS Price
Identifying No.
Grant-Number-R01-OH-008282
Issue of Publication
1
ISSN
0167-594X
Source Name
Journal of Neuro-Oncology
State
PA
Performing Organization
University of Pittsburgh at Pittsburgh
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