Cold atmospheric nitrogen plasma induces metal-initiated cell death by cell membrane rupture and mitochondrial perturbation.

Cold atmospheric plasma (CAP) is a novel biomedical tool used for cancer therapy. A device using nitrogen gas (N 2 CAP) produced CAP that induced cell death through the production of reactive nitrogen species and an increase in intracellular calcium. In this study, we investigated the effect of N 2 CAP-irradiation on cell membrane and mitochondrial function in human embryonic kidney cell line 293T. We investigated whether iron is involved in N 2 CAP-induced cell death, as deferoxamine methanesulfonate (an iron chelator) inhibits this process. We found that N 2 CAP induced cell membrane disturbance and loss of mitochondrial membrane potential in an irradiation time-dependent manner. BAPTA-AM, a cell-permeable calcium chelator, inhibited N 2 CAP-induced loss of mitochondrial membrane potential. These results suggest that disruption of intracellular metal homeostasis was involved in N 2 CAP-induced cell membrane rupture and mitochondrial dysfunction. Moreover, N 2 CAP irradiation generated a time-dependent production of peroxynitrite. However, lipid-derived radicals are unrelated to N 2 CAP-induced cell death. Generally, N 2 CAP-induced cell death is driven by the complex interaction between metal movement and reactive oxygen and nitrogen species produced by N 2 CAP.