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

Details

• Personal Author:
  Belikova NA ; Huang Z ; Jiang J ; Kagan VE ; Mintz AH ; Stoyanovsky DA
• Description:
  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. [Description provided by NIOSH]
• Subjects:
  Antioxidants Lymphocyte Activation Neoplasms Nervous System Nervous System Diseases Nitrogen Oxides Occupational Health Radiation Safety
• Keywords:
  Apoptosis Author Keywords: Glioblastoma Blastogenesis Brain-tumors Cancer Cell-alteration Cellular-structures Chemotherapy Gamma-irradiation Hydrophobic-bonds Irradiation Medical-treatment Mitochondria Nitrogen-oxides Oncogenic-agents Radiation-therapy Radiobiology Survival-rate Triphenyl-phosphonium Conjugated Nitroxide Tumors

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• ISSN:
  0167-594X
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  OSHA Region 3 ; Pennsylvania
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  1-8
• Volume:
  100
• Issue:
  1
• NIOSHTIC Number:
  nn:20037966
• Citation:
  J Neuro-Oncol 2010 Oct; 100(1):1-8
• Contact Point Address:
  Arlan H. Mintz, Department of Neurosurgery, University of Pittsburgh, Cancer Pavillion, Shadyside Hospital, 5150 Center Avenue, Suite 430, Pittsburgh, PA 15232, USA
• Email:
  mintzah@upmc.edu
• Federal Fiscal Year:
  2011
• NORA Priority Area:
  Manufacturing
• Performing Organization:
  University of Pittsburgh at Pittsburgh
• Peer Reviewed:
  True
• Start Date:
  20050701
• Source Full Name:
  Journal of Neuro-Oncology
• End Date:
  20160630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:1847c09d35473455bd43a69493cbf83998ae6b0abcea6ef67a7396021725c088e2539e2d7103bbfc554ded6b229637b67d9eb609a69187c7dc37c5742909bbe4
• Download URL:
  https://stacks.cdc.gov/view/cdc/191864/cdc_191864_DS1.pdf
• File Type:
  [PDF - 492.63 KB ]