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 γ-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 γ-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.

Biroccio, A., Benassi, B., Filomeni, G., Amodei, S., Marchini, S., Chiorino, G., et al. (2002). Glutathione influences c-Myc-induced apoptosis in M14 human melanoma cells. JOURNAL OF BIOLOGICAL CHEMISTRY, 277(46), 43763-43770 [10.1074/jbc.M207684200].

Glutathione influences c-Myc-induced apoptosis in M14 human melanoma cells

FILOMENI, GIUSEPPE;ROTILIO, GIUSEPPE;CIRIOLO, MARIA ROSA
2002-01-01

Abstract

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 γ-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 γ-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.
2002
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore BIO/10 - BIOCHIMICA
English
Con Impact Factor ISI
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
Biroccio, A., Benassi, B., Filomeni, G., Amodei, S., Marchini, S., Chiorino, G., et al. (2002). Glutathione influences c-Myc-induced apoptosis in M14 human melanoma cells. JOURNAL OF BIOLOGICAL CHEMISTRY, 277(46), 43763-43770 [10.1074/jbc.M207684200].
Biroccio, A; Benassi, B; Filomeni, G; Amodei, S; Marchini, S; Chiorino, G; Rotilio, G; Zupi, G; Ciriolo, Mr
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/54033
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