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Cold atmospheric plasma (CAP) is a rapidly developed technology that has been widely applied in biomedicine especially in cancer treatment. Due to the generation of various active species in plasma, CAP could induce various tumor cells death and showed a promising potential in cancer therapy. To enhance the biological effects of gas plasma, changing the discharging parameters is the most commonly used method, yet increasing discharging power will lead to a higher possibility of simultaneously damage surrounding tissues. In this study, by adding nontoxic concentration of additional nitrite and nitrate in the medium, we found that anti-tumor effect of CAP treatment was enhanced in the same discharging parameters. By microplate reader and cell flow cytometer we measured several extracellular and intracellular RONS and found that ONOO- was mostly correlated with the enhanced cancer cell killing effect. We proposed that more nitrogen supplies such as nitrite and nitrate could increase the production of RNS especially ONOO- and resulted in a better killing effect to cancer cells. Our results provided a new strategy to enhance the antitumor effect by plasma jet treatment without changing the discharging parameters.Cold atmospheric plasma (CAP) is a rapidly developed technology that has been widely applied in biomedicine especially in cancer treatment. Due to the generation of various active species in plasma, CAP could induce various tumor cells death and showed a promising potential in cancer therapy. To enhance the biological effects of gas plasma, changing the discharging parameters is the most commonly used method, yet increasing discharging power will lead to a higher possibility of simultaneously damage surrounding tissues. In this study, by adding nontoxic concentration of additional nitrite and nitrate in the medium, we found that anti-tumor effect of CAP treatment was enhanced in the same discharging parameters. By microplate reader and cell flow cytometer we measured several extracellular and intracellular RONS and found that ONOO- was mostly correlated with the enhanced cancer cell killing effect. We proposed that more nitrogen supplies such as nitrite and nitrate could increase the production of RNS esp...

NO2- and NO3- enhance cold atmospheric plasma induced cancer cell death by generation of ONOO-