CNP mediated selective toxicity on melanoma cells is accompanied by mitochondrial dysfunction

Autoři: Elif Aplak aff001;  Claudia von Montfort aff001;  Lisa Haasler aff001;  David Stucki aff001;  Bodo Steckel aff002;  Andreas S. Reichert aff001;  Wilhelm Stahl aff001;  Peter Brenneisen aff001
Působiště autorů: Institute of Biochemistry and Molecular Biology I, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany aff001;  Department of Molecular Cardiology, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany aff002
Vyšlo v časopise: PLoS ONE 15(1)
Kategorie: Research Article


Cerium (Ce) oxide nanoparticles (CNP; nanoceria) are reported to have cytotoxic effects on certain cancerous cell lines, while at the same concentration they show no cytotoxicity on normal (healthy) cells. Redox-active CNP exhibit both selective prooxidative as well as antioxidative properties. The former is proposed to be responsible for impairment of tumor growth and invasion and the latter for rescuing normal cells from reactive oxygen species (ROS)-induced damage. Here we address possible underlying mechanisms of prooxidative effects of CNP in a metastatic human melanoma cell line. Malignant melanoma is the most aggressive form of skin cancer, and once it becomes metastatic the prognosis is very poor. We have shown earlier that CNP selectively kill A375 melanoma cells by increasing intracellular ROS levels, whose basic amount is significantly higher than in the normal (healthy) counterpart, the melanocytes. Here we show that CNP initiate a mitochondrial increase of ROS levels accompanied by an increase in mitochondrial thiol oxidation. Furthermore, we observed CNP-induced changes in mitochondrial bioenergetics, dynamics, and cristae morphology demonstrating mitochondrial dysfunction which finally led to tumor cell death. CNP-induced cell death is abolished by administration of PEG-conjugated catalase. Overall, we propose that cerium oxide nanoparticles mediate cell death via hydrogen peroxide production linked to mitochondrial dysfunction.

Klíčová slova:

Hydrogen peroxide – Melanocytes – Melanoma cells – Membrane potential – Mitochondria – Oxidation – Thiols – Superoxides


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