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 Î³-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 Î³-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.
|Tipologia:||Articolo su rivista|
|Citazione:||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.|
|IF:||Con Impact Factor ISI|
|Settore Scientifico Disciplinare:||Settore BIO/10|
|Revisione (peer review):||Sì, ma tipo non specificato|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1074/jbc.M207684200|
|Stato di pubblicazione:||Pubblicato|
|Data di pubblicazione:||2002|
|Titolo:||Glutathione influences c-Myc-induced apoptosis in M14 human melanoma cells|
|Autori:||Biroccio, A; Benassi, B; FILOMENI, G; Amodei, S; Marchini, S; Chiorino, G; ROTILIO, G; Zupi, G; CIRIOLO, MR|
|Appare nelle tipologie:||01 - Articolo su rivista|