Distinct biological actions of electrical and chemical factors of cold atmospheric pressure plasma and their synergistic cytotoxic effects

Cold atmospheric pressure plasma (CAP) is recently regarded as a novel means for cancer therapy, because of its prominent cytotoxicity. The combined effects of electrical and chemical factors of CAP have been considered to achieve the cytotoxicity. Whereas reactive species are well known to be important for the CAP cytotoxicity, the biological significance of electrical factors of CAP remains largely unclear. In this study, we analyzed cytotoxic effects of a combination of electrical and chemical factors of CAP on the human fibrosarcoma HT-1080 cells. When cells were incubated in CAP-exposed solution that contained substantial levels of H₂O₂ and NO₂₋, their viability was markedly decreased. In the absence of effects of reactive species, electrical factors of CAP did not show any adverse influences on cells. Interestingly, CAP-exposed solution exhibited more cytotoxicity on the electrically stimulated cells than unstimulated ones. This observation suggests that the electrical stimulation altered the nature of cells and increased cell susceptibility to CAP-exposed solution. Taken together, our findings reveal a novel aspect of the biological action of electrical factors, which is mechanistically distinct from that of reactive species, and demonstrate that electrical and chemical factors of CAP synergistically act on cells to achieve high cytotoxicity.