Synergistic Effect of H(2)O(2) and NO(2) in Cell Death Induced by Cold Atmospheric He Plasma

Cold atmospheric pressure plasmas (CAPPs) have emerged over the last decade as a new promising therapy to fight cancer. CAPPs’ antitumor activity is primarily due to the delivery of reactive oxygen and nitrogen species (RONS), but the precise determination of the constituents linked to this anticancer process remains to be done. In the present study, using a micro-plasma jet produced in helium (He), we demonstrate that the concentration of H(2)O(2), NO(2)(−) and NO(3)(−) can fully account for the majority of RONS produced in plasma-activated buffer. The role of these species on the viability of normal and tumour cell lines was investigated. Although the degree of sensitivity to H(2)O(2) is cell-type dependent, we show that H(2)O(2) alone cannot account for the toxicity of He plasma. Indeed, NO(2)(−), but not NO(3)(−), acts in synergy with H(2)O(2) to enhance cell death in normal and tumour cell lines to a level similar to that observed after plasma treatment. Our findings suggest that the efficiency of plasma treatment strongly depends on the combination of H(2)O(2) and NO(2)(−) in determined concentrations. We also show that the interaction of the He plasma jet with the ambient air is required to generate NO(2)(−) and NO(3)(−) in solution.