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

Annamaria Biroccio, Barbara Benassi, Giuseppe Filomeni, Sarah Amodei, Sergio Marchini, Giovanna Chiorino, Giuseppe Rotilio, Gabriella Zupi, Maria Rosa Ciriolo

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)43763-43770
Number of pages8
JournalJournal of Biological Chemistry
Volume277
Issue number46
DOIs
Publication statusPublished - Nov 15 2002

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Glutathione
Melanoma
Down-Regulation
Glutathione Disulfide
Cell death
Ligases
Apoptosis
Cysteine
Oxidoreductases
Cell Death
Caspase 9
Doxycycline
Acetylcysteine
Enzyme activity
Cytochromes c
NADP
Metabolism
Gene expression
Caspase 3
Cytosol

ASJC Scopus subject areas

  • Biochemistry

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Glutathione influences c-Myc-induced apoptosis in M14 human melanoma cells. / Biroccio, Annamaria; Benassi, Barbara; Filomeni, Giuseppe; Amodei, Sarah; Marchini, Sergio; Chiorino, Giovanna; Rotilio, Giuseppe; Zupi, Gabriella; Ciriolo, Maria Rosa.

In: Journal of Biological Chemistry, Vol. 277, No. 46, 15.11.2002, p. 43763-43770.

Research output: Contribution to journalArticle

Biroccio, Annamaria ; Benassi, Barbara ; Filomeni, Giuseppe ; Amodei, Sarah ; Marchini, Sergio ; Chiorino, Giovanna ; Rotilio, Giuseppe ; Zupi, Gabriella ; Ciriolo, Maria Rosa. / Glutathione influences c-Myc-induced apoptosis in M14 human melanoma cells. In: Journal of Biological Chemistry. 2002 ; Vol. 277, No. 46. pp. 43763-43770.
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