Mechanistic insights into the impact of cold atmospheric pressure plasma on human epithelial cell lines
Résumé
Compelling evidence suggests that Cold Atmospheric Pressure Plasma (CAPPs) has potential as a new cancer therapy. However, knowledge about cellular signaling events and toxicity subsequent to plasma treatment of is still poorly documented. The aim of this study was to focus on the interaction between 3 different types of plasma (He, He-O2, He-N2) and human epithelial cell lines to gain better insight into plasma-cell interaction. We choose epithelial cell lines (human keratinocytes, human fibroblasts, human colorectal carcinoma and skin melanoma) to gain insight into plasma-cell interaction and to determine which cellular pathways are induced by CAPP treatment in normal and malignant cells. We provide evidence that the proteasome, a major intracellular proteolytic system which is important for tumor cell growth and survival, is a target for (He or He-N2) CAPP. This is accompanied by apoptosis, DNA damage, mitochondrial dysfunction and mild oxidative protein damage. By differential label-free quantitative proteomic analysis we found that CAPP triggers antioxidant and cellular defense but also seen cancerous processes in keratinocytes. Moreover we found that malignant cells are more resistant to CAPP treatment than normal cells. However, reactiveoxygen and nitrogen species (RONS) are not the only actors involved in cell death; electric field and charged particles could play a significant role especially for He-O2 CAPP. Particular attention was paid to the contribution of the electric field (EF) and RONS in cellular response to plasma treatment. Taken together, our findings provide insight into potential mechanisms of CAPP-induced cell death.