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

Autor: von Montfort C; Institute of Biochemistry and Molecular Biology I, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany., Aplak E; Institute of Biochemistry and Molecular Biology I, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany., Ebbert L; Institute of Biochemistry and Molecular Biology I, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany., Wenzel CK; Institute of Biochemistry and Molecular Biology I, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany., Klahm NP; Institute of Biochemistry and Molecular Biology I, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany., Stahl W; Institute of Biochemistry and Molecular Biology I, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany., Brenneisen P; Institute of Biochemistry and Molecular Biology I, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2024 Mar 21; Vol. 19 (3), pp. e0300718. Date of Electronic Publication: 2024 Mar 21 (Print Publication: 2024).
DOI: 10.1371/journal.pone.0300718
Abstrakt: 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 the patients. Shown by us earlier, cerium oxide nanoparticles (CNP, nanoceria) selectively killed A375 melanoma cells while not being cytotoxic at identical concentrations on non-cancerous cells. In conclusion, the redox-active CNP exhibited both prooxidative as well as antioxidative properties. In that context, CNP induced mitochondrial dysfunction in the studied melanoma cells via generation of reactive oxygene species (primarily hydrogen peroxide (H2O2)), but that does not account for 100% of the toxicity.
Aim: Cancer cells often show an increased glycolytic rate (Warburg effect), therefore we focused on CNP mediated changes of the glucose metabolism.
Results: It has been shown before that glyceraldehyde 3-phosphate dehydrogenase (GAPDH) activity is regulated via oxidation of a cysteine in the active center of the enzyme with a subsequent loss of activity. Upon CNP treatment, formation of cellular lactate and GAPDH activity were significantly lowered. The treatment of melanoma cells and melanocytes with the GAPDH inhibitor heptelidic acid (HA) decreased viability to a much higher extent in the cancer cells than in the studied normal (healthy) cells, highlighting and supporting the important role of GAPDH in cancer cells.
Conclusion: We identified glyceraldehyde 3-phosphate dehydrogenase (GAPDH) as a target protein for CNP mediated thiol oxidation.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: © 2024 von Montfort et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje