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Malate-aspartate shuttle inhibitor aminooxyacetic acid leads to decreased intracellular ATP levels and altered cell cycle of C6 glioma cells by inhibiting glycolysis.
- Source :
-
Cancer Letters . Aug2016, Vol. 378 Issue 1, p1-7. 7p. - Publication Year :
- 2016
-
Abstract
- NADH shuttles, including malate-aspartate shuttle (MAS) and glycerol-3-phosphate shuttle, can shuttle the reducing equivalents of cytosolic NADH into mitochondria. It is widely accepted that the major function of NADH shuttles is to increase mitochondrial energy production. Our study tested the hypothesis that the novel major function of NADH shuttles in cancer cells is to maintain glycolysis by decreasing cytosolic NADH/NAD(+) ratios. We found that AOAA, a widely used MAS inhibitor, led to decreased intracellular ATP levels, altered cell cycle and increased apoptosis and necrosis of C6 glioma cells, without affecting the survival of primary astrocyte cultures. AOAA also decreased the glycolytic rate and the levels of extracellular lactate and pyruvate, without affecting the mitochondrial membrane potential of C6 cells. Moreover, the toxic effects of AOAA were completely prevented by pyruvate treatment. Collectively, our study has suggested that AOAA may be used to selectively decrease glioma cell survival, and the major function of MAS in cancer cells may be profoundly different from its major function in normal cells: The major function of MAS in cancer cells is to maintain glycolysis, instead of increasing mitochondrial energy metabolism. [ABSTRACT FROM AUTHOR]
- Subjects :
- *ADENOSINE triphosphate
*GLIOMAS
*GLYCOLYSIS
*MITOCHONDRIA
*CELL cycle
*ASPARTIC acid metabolism
*CELL metabolism
*ADENOSINE triphosphate metabolism
*ANIMALS
*ANTINEOPLASTIC agents
*APOPTOSIS
*BIOCHEMISTRY
*BIOLOGICAL transport
*CELL culture
*CELL lines
*CELLS
*CELLULAR signal transduction
*DOSE-effect relationship in pharmacology
*PHENOMENOLOGY
*MEMBRANE proteins
*NECROSIS
*RATS
*HYDROXY acids
*MEMBRANE transport proteins
*PHARMACODYNAMICS
Subjects
Details
- Language :
- English
- ISSN :
- 03043835
- Volume :
- 378
- Issue :
- 1
- Database :
- Academic Search Index
- Journal :
- Cancer Letters
- Publication Type :
- Academic Journal
- Accession number :
- 115594804
- Full Text :
- https://doi.org/10.1016/j.canlet.2016.05.001