Cellular thiol pool and redox buffering systems

The cellular thiol pool and redox buffering systems, primarily comprising the glutathione (GSH) and thioredoxin (Trx) pathways, are essential for maintaining intracellular redox homeostasis and protecting cells from oxidative damage [PMID: 28410660]. In cisplatin-resistant ovarian cancer, these systems are frequently upregulated, providing a robust defense against the cytotoxic effects of platinum-based therapies [PMID: 12664238]. Cisplatin functions by forming DNA adducts that trigger apoptosis, but elevated levels of thiols like GSH can directly conjugate with cisplatin, facilitating its export via multidrug resistance-associated proteins (MRPs) and preventing DNA damage [PMID: 15546595]. Additionally, the Trx system helps repair oxidative damage and inhibits apoptosis-regulating signal kinase 1 (ASK1), further promoting cell survival [PMID: 27634440]. Pharmacological strategies to overcome resistance involve the use of agents like buthionine sulfoximine (BSO) to deplete GSH or auranofin to inhibit thioredoxin reductase, thereby sensitizing cancer cells to cisplatin [PMID: 3115984, 28410660]. However, the clinical application of these inhibitors is often limited by the potential for systemic toxicity, as these redox systems are vital for the survival of normal cells [PMID: 12664238].

Other names

Antioxidant defense systemThiol-mediated redox systemGSH/Trx systemsThiol-dependent antioxidant systemRedox buffering network

Inhibition of glutathione synthesis, inhibition of thioredoxin reductase activity, and inhibition of glutathione S-transferase to increase intracellular oxidative stress and prevent the detoxification of cisplatin [PMID: 12664238, 28410660].