Definition

A naturally-occurring, sulfur-rich, cyclic oligopeptide antibiotic of the thiopeptide class, and an irreversible inhibitor of the mitochondrial thioredoxin-dependent peroxide reductase (peroxiredoxin-3; PRX3; antioxidant protein 1; AOP-1), with potential antineoplastic activity. Upon intrapleural administration, thiostrepton irreversibly binds to and inhibits the activity of PRX3. This inhibits the peroxidase activity of the thioredoxin reductase 2 (TXNRD2)-thioredoxin-2 (TRX2)-PRX3 antioxidant signaling network within the mitochondria, which may result in the accumulation of hydrogen peroxide and lead to tumor cell death. PRX3 is upregulated in cancer cells and plays an important role in the regulation of the oxidative stress pathways.