Extracellular hydrogen peroxide generation

Extracellular hydrogen peroxide (H2O2) generation is a pro-oxidant therapeutic strategy rather than a specific molecular target like a receptor or enzyme. This approach primarily utilizes pharmacological doses of intravenous Ascorbic acid (Vitamin C), which reacts with transition metal ions (such as iron or copper) in the interstitial fluid to generate H2O2 (Chen et al., 2005, PNAS). While normal cells possess robust antioxidant defenses, many cancer cell lines exhibit a relative deficiency in H2O2-detoxifying enzymes, particularly catalase, making them selectively vulnerable to oxidative stress (Schoenfeld et al., 2017, Cancer Cell). The resulting influx of H2O2 into the cytoplasm leads to DNA damage, depletion of ATP, and activation of cell death pathways such as apoptosis or necrosis. This mechanism is currently being investigated in clinical trials as an adjuvant to standard chemotherapy and radiation to enhance tumor killing while sparing healthy tissue (NIH/NCI, 2023).

Other names

Pro-oxidant therapyPharmacological ascorbate-mediated H2O2 productionExtracellular ROS generationAscorbate-induced oxidative stress

Drugs act as pro-drugs or catalysts in the extracellular space to generate high concentrations of hydrogen peroxide (H2O2), which then diffuses into target cells to induce oxidative damage and metabolic collapse.