KEY TAKEAWAYS
- The study aimed to investigate the selective toxicity mechanism of CNP in melanoma cells, focusing on the role of GAPDH and its implications for targeted cancer therapy.
- Researchers noticed that GAPDH serves as a target protein for CNP-mediated thiol oxidation, shedding light on a potential mechanism underlying CNP-induced selective toxicity in melanoma cells.
Malignant melanoma, characterized with the aid of its aggressiveness and bad analysis, poses huge demanding situations in remedy, specifically because of the severe aspect outcomes associated with standard chemotherapy. Previous research has demonstrated the selective cytotoxicity of cerium oxide nanoparticles (CNP, nanoceria) inside the route of A375 melanoma cells at the same time as sparing non-cancerous cells at identical concentrations.
This selectivity highlights the potential of CNPs as targeted drug therapies. Furthermore, the dual nature of CNP as both prooxidative and antioxidant has been observed, indicating a complex role in cellular redox processes. Despite inducing mitochondrial dysfunction through the generation of reactive oxygen species (ROS), especially hydrogen peroxide (H2O2) in melanoma cells, this pathway does not show the observed toxicities completely.
Claudia von Montfort and the team aimed to assess the underlying mechanism of CNP-induced selective toxicity in melanoma cells, with a particular focus on the role of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and its implications for targeted cancer therapy.
The analysis revealed that GAPDH activity is regulated by the oxidation of a cysteine in the enzyme’s active center, leading to decreased activity. Following treatment with CNP, there was a notable reduction in cellular lactate production and GAPDH activity.
Moreover, administering the GAPDH inhibitor heptelidic acid (HA) to melanoma cells and melanocytes resulted in a significantly higher decrease in viability among cancer cells compared to normal cells. This underscores the pivotal role of GAPDH in cancer cells, further supported by the findings.
The study concluded that GAPDH is a target protein for CNP-mediated thiol oxidation, highlighting a crucial mechanism underlying CNP-induced selective toxicity in melanoma cells.
The study is sponsored by Deutsche Forschungsgemeinschaft.
Source: https://pubmed.ncbi.nlm.nih.gov/38512909/
von Montfort C, Aplak E, Ebbert L, et al. (2024). “The role of GAPDH in the selective toxicity of CNP in melanoma cells.” PLoS One. 2024 Mar 21;19(3):e0300718. doi: 10.1371/journal.pone.0300718. PMID: 38512909; PMCID: PMC10956844.
