Differential Sensitivity of Melanoma Cells and Their Non-Cancerous Counterpart to Cold Atmospheric Plasma-Induced Reactive Oxygen and Nitrogen Species

Despite continuous progress in therapy, melanoma is one of the most aggressive and malignant human tumors, often relapsing and metastasizing to almost all organs. Cold atmospheric plasma (CAP) is a novel anticancer tool that utilizes abundant reactive oxygen and nitrogen species (RONS) being deposited on the target cells and tissues. CAP-induced differential effects between non-cancerous and cancer cells were comparatively examined. Melanoma and non-cancerous skin fibroblast cells (counterparts; both cell types were isolated from the same patient) were used for plasma-cell interactions. The production of intracellular RONS, such as nitric oxide (NO), hydroxyl radical (•OH), and hydrogen peroxide (H₂O₂), increased remarkably only in melanoma cancer cells. It was observed that cancer cells morphed from spread to round cell shapes after plasma exposure, suggesting that they were more affected than non-cancerous cells in the same plasma condition. Immediately after both cell types were treated with plasma, there were no differences in the amount of extracellular H₂O₂ production, while Hanks' balanced salt solution-containing cancer cells had lower concentrations of H₂O₂ than that of non-cancerous cells at 1 h after treatment. The melanoma cells seemed to respond to CAP treatment with a greater rise in RONS and a higher consumption rate of H₂O₂ than homologous non-cancerous cells. These results suggest that differential sensitivities of non-cancerous skin and melanoma cells to CAP-induced RONS can enable the applicability of CAP in anticancer therapy.