Synergistic Effect of H2O2 and NO2 in Cell Death Induced by Cold Atmospheric He Plasma.

Pierre-Marie Girard,João Santos Sousa,Atousa Arbabian,Michel Fleury,Marie Dutreix,Gérard Bauville,Vincent Puech

doi:10.1038/srep29098

Abstract

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 H2O2, NO2− and NO3− 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 H2O2 is cell-type dependent, we show that H2O2 alone cannot account for the toxicity of He plasma. Indeed, NO2−, but not NO3−, acts in synergy with H2O2 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 H2O2 and NO2− in determined concentrations. We also show that the interaction of the He plasma jet with the ambient air is required to generate NO2− and NO3− in solution.

Highlights

Can be generated in or transferred into the liquid phase surrounding the biological target[16,17]
Because plasma treatment leads to the formation of nitrite (NO2−) and nitrate (NO3−) in solution[16,17], we checked that there was no change in the absorbance at 260 and 270 nm of 1 mM Na3VO4 incubated in the presence of either NaNO2 or NaNO3 for concentrations up to 3 mM
As we previously demonstrated that approximately 400 μM of H2O2, 400 μM of NO2− and 100 μM of NO3− are generated per minute of He plasma treatment at a gas flow of 50 sccm, we looked at the absorbance of a mixed solution of 800 μM of H2O2, 800 μM of NO2− and 200 μM of NO3− (Fig. 4D)

Summary

Introduction

Can be generated in or transferred into the liquid phase surrounding the biological target[16,17]. The aim of this study was to identify the main long-lived reactive species generated in a simple buffered solution by a He plasma jet operating in ambient air at low gas flow, and their contribution to the plasma-induced cell death in normal and cancer cell lines

Objectives

Methods

Results

Conclusion