Glutathione Influences c-Myc-induced Apoptosis in M14 Human Melanoma Cells
Copyright policy )Glutathione Influences c-Myc-induced Apoptosis in M14 Human Melanoma Cells
The objective of this article is to dissect the mechanisms by which the down-regulation of c-Myc induces programmed cell death in melanoma cells. In stable and doxycycline-inducible M14 melanoma cells, down-regulation of c-Myc induced apoptosis subsequent to a decrease in the intracellular reduced glutathione content and a concomitant accumulation of its oxidized form. This redox alteration was associated with a decrease of the enzyme activities of gamma-glutamyl-cysteine synthetase and NADPH-dependent GSSG reductase, as well as a consequent glutathione release in the extracellular medium. Cytochrome c was released into the cytosol at very early stages of apoptosis induction, long before detectable production of reactive oxygen species and activation of caspase-9 and -3. Macroarray analysis revealed that down-regulation of c-Myc produced striking changes in gene expression in the section related to metabolism, where the expression of gamma-glutamyl-cysteine synthetase and GSSG reductase was found to be significantly reduced. The addition of N-acetyl-l-cysteine or glutathione ethyl ester inhibited the apoptotic process, thus confirming the key role of glutathione in programmed cell death induced by c-Myc.
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Apoptosis, reactive oxygen metabolite, Cytosol, caspase 3, NADH, NADPH Oxidoreductases, glutathione, caspase 9, Melanoma, Oligonucleotide Array Sequence Analysis, glutamate cysteine ligase, oncogene c myc, Blotting, Caspase 3, article, Flow Cytometry, Glutathione, Caspase 9, enzyme activity, Anti-Bacterial Agents, cytochrome c, glutathione ethyl ester, Glutathione Reductase, priority journal, Caspases, Doxycycline, Western, NADPH Oxidoreductase, melanoma cell, Glutamate-Cysteine Ligase, Blotting, Western, Down-Regulation, Cytochrome c Group, Proto-Oncogene Proteins c-myc, Oxidation, acetylcysteine, Anti-Bacterial Agent, reduced nicotinamide adenine dinucleotide phosphate, Humans, controlled study, human, glutathione reductase, Enzymes; Genetic engineering; Metabolism; Oxidation; Apoptosis; Cells; acetylcysteine; caspase 3; caspase 9; cytochrome c; glutamate cysteine ligase; glutathione; glutathione ethyl ester; glutathione reductase; reactive oxygen metabolite; reduced nicotinamide adenine dinucleotide phosphate; apoptosis; article; controlled study; enzyme activation; enzyme activity; gene expression; human; human cell; melanoma cell; metabolism; oncogene c myc; oxidation reduction reaction; priority journal; Anti-Bacterial Agents; Apoptosis; Blotting, Western; Caspase 3; Caspase 9; Caspases; Cytochrome c Group; Cytosol; Down-Regulation; Doxycycline; Flow Cytometry; Glutamate-Cysteine Ligase; Glutathione; Glutathione Reductase; Humans; Melanoma; NADH, NADPH Oxidoreductases; Oligonucleotide Array Sequence Analysis; Proto-Oncogene Proteins c-myc; Reactive Oxygen Species; Time Factors; Tumor Cells, Cultured, Oligonucleotide Array Sequence Analysi, human cell, Apoptosi, enzyme activation, Caspase, Metabolism, Enzyme, Genetic engineering, NADH, gene expression, Cell, Reactive Oxygen Species, oxidation reduction reaction
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