Partially ionized gas, also known as cold atmospheric plasma (CAP), is reported to have anti-tumor specific properties via reactive oxygen and nitrogen species (RONS) in different tumor entities. Many CAP effects have already been studied, but the exact influence on metabolism has yet to be defined.

Analyses of metabolic substrates, metabolic pathways, genes, mRNA and nitration were performed to investigate CAP-treated and untreated melanoma and non-malignant cells.

We discovered a dose-dependent downregulation of oxidative phosphorylation and glycolysis in CAP-treated compared to untreated melanoma cells, whereas for non-malignant cells we saw no change in the oxidative phosphorylation and even an increase in the glycolysis. Gene set enrichment analyses demonstrated a downregulation of gene sets associated with metabolic processes in melanoma cells. These effects could be explained by posttranslational modification via tyrosine nitration, induced by RONS. A higher induction of protein nitration was found in CAP-treated melanoma cells opposed to non-malignant cells. This difference may contribute to the antitumor-specific effects of CAP.

This study shows different molecular and metabolic responses of melanoma and non-malignant cells in vitro. It thereby contributes to a better understanding of the antitumor-specific effects of CAP and facilitates the development of CAP-based treatments.