Inhibition of thioredoxin reductase by auranofin induces apoptosis in cisplatin-resistant human ovarian cancer cells

Cisplatin is an effective antitumor agent for the treatment of several carcinomas

Christine Marzano; Valentina Gandin; Alessandra Folda; Guido Scutari; Alberto Bindoli; Maria Pia Rigobello

2006

Scholarcy highlights

  • Cisplatin is an effective antitumor agent for the treatment of several carcinomas
  • Auranofin is more effective than cisplatin in decreasing cell viability and its action is marked in C13* cells, indicating that no cross-resistance occurs
  • Treatment with auranofin determines a consistent release of cytochrome c in both cell lines, while cisplatin is effective only in sensitive cells
  • Apoptosis is accompanied by an increased production of hydrogen peroxide that, is inhibited by N-acetyl-L-cysteine
  • H2O2 production is counteracted by a large overexpression of thioredoxin reductase that constitutes the preferred target of the inhibitory action of auranofin
  • This specific effect of auranofin might rationalize its ability in overcoming cisplatin resistance in human ovarian cancer cells

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