The role of GAPDH in the selective toxicity of CNP in melanoma cells

• DOI: 10.1371/journal.pone.0300718
• Publication Date: 2024-03-21T17:40:40Z
• Authors: Claudia von Montfort; Elif Aplak; Lara Ebbert; Chantal-Kristin W...; Niklas P. Klahm; Wilhelm Stahl; Peter Brenneisen
• Keywords: Glyceraldehyde 3-phosphate dehydrogenase; Glyceraldehyde; Warburg Effect

Background Malignant melanoma is the most aggressive form of skin cancer with a rather poor prognosis. Standard chemotherapy often results in severe side effects on normal (healthy) cells finally being difficult to tolerate for patients. Shown by us earlier, cerium oxide nanoparticles (CNP, nanoceria) selectively killed A375 while not cytotoxic at identical concentrations non-cancerous cells. In conclusion, redox-active CNP exhibited both prooxidative as well antioxidative properties. that context, induced mitochondrial dysfunction studied via generation reactive oxygene species (primarily hydrogen peroxide (H 2 O )), but does account 100% toxicity. Aim Cancer show an increased glycolytic rate (Warburg effect), therefore we focused mediated changes glucose metabolism. Results It has been shown before glyceraldehyde 3-phosphate dehydrogenase (GAPDH) activity regulated oxidation cysteine active center enzyme subsequent loss activity. Upon treatment, formation cellular lactate and GAPDH were significantly lowered. The treatment melanocytes inhibitor heptelidic acid (HA) decreased viability much higher extent than cells, highlighting supporting important role Conclusion We identified target protein thiol oxidation.