Journal article
Pharmacologic manipulations of mitochondrial membrane potential (ΔΨm) selectively in glioma cells
Journal of neuro-oncology, Vol.81(1), pp.9-20
01/2007
DOI: 10.1007/s11060-006-9201-6
PMID: 16862448
Abstract
Metabolic control theory applies principles of bioenergetics for the control or management of complex diseases. Since metabolism is a general process underlying all biologic phenotypes, changes in metabolism can potentially modify phenotype. Therefore, it is reasonable to assume that experimental modulation of the availability of cellular energy can potentially alter cell phenotypes and cell functions critical to tumor progression including cell division. The purpose of this study was to determine if OMX-2, a methylquinone system designed to shuttle electrons from mitochondrial complexes, was able to target mitochondria in cancer cells and trigger cell death. Using flow cytometry, cell viability assays, and ATP measurements, we found that OMX-2 differentially decreased ΔΨm without triggering cell death. In contrast, known blockers of the Electron Transport Chain (ETC) decreased ΔΨm and triggered cell death. When normal cells were treated with OMX-2, neither ΔΨm or cell death was triggered. Furthermore, OMX-2 modulated intracellular ATP and decreased cell numbers of glioma cells. Cell cycle analysis indicated that OMX-2 induced a reversible cell cycle arrest in G1/S. Finally, impairment of glycolysis by 2-Deoxyglucose (2-DOG) acted synergistically with OMX-2 to trigger cell death. Overall, these results indicate that it is possible to selectively target cancer cells by decreasing ΔΨm and induced cell cycle arrest without triggering cell death. Moreover, pharmacological approaches designed to act on both glycolysis and oxidative phosphorylation can be considered as a new approach to selectively kill cancer cells.
Details
- Title: Subtitle
- Pharmacologic manipulations of mitochondrial membrane potential (ΔΨm) selectively in glioma cells
- Creators
- Corinne Griguer - Department of Surgery University of Alabama at Birmingham 1918 University Blvd., THT 1046 Birmingham AL 35294-0006 USAClaudia Oliva - Department of Surgery University of Alabama at Birmingham 1918 University Blvd., THT 1046 Birmingham AL 35294-0006 USAG. Yancey Gillespie - Department of Surgery University of Alabama at Birmingham 1918 University Blvd., THT 1046 Birmingham AL 35294-0006 USAEric Gobin - Service d'Anatomie Pathologique Centre Hospitalier Universitaire Morvan 29609 Brest FrancePascale Marcorelles - Service d'Anatomie Pathologique Centre Hospitalier Universitaire Morvan 29609 Brest France
- Resource Type
- Journal article
- Publication Details
- Journal of neuro-oncology, Vol.81(1), pp.9-20
- Publisher
- Kluwer Academic Publishers-Plenum Publishers; New York
- DOI
- 10.1007/s11060-006-9201-6
- PMID
- 16862448
- ISSN
- 0167-594X
- eISSN
- 1573-7373
- Language
- English
- Date published
- 01/2007
- Academic Unit
- Radiation Oncology
- Record Identifier
- 9984047635702771
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