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The synergistic effect between hydrogen peroxide and nitrite, two long-lived molecular species from cold atmospheric plasma, triggers tumor cells to induce their own cell death.

ABSTRACT: Nitrite and H2O2 are long-lived species in cold atmospheric plasma and plasma-activated medium. It is known that their synergistic interaction is required for selective apoptosis induction in tumor cells that are treated with plasma-activated medium. This study shows that the interaction between nitrite and H2O2 leads to the formation of peroxynitrite, followed by singlet oxygen generation through the interaction between peroxynitrite and residual H2O2. This primary singlet oxygen causes local inactivation of few catalase molecules on the surface of tumor cells. As a consequence, H2O2 and peroxynitrite that are constantly produced by tumor cells and are usually decomposed by their protective membrane-associated catalase, are surviving at the site of locally inactivated catalase. This leads to the generation of secondary singlet oxygen through the interaction between tumor cell-derived H2O2 and peroxynitrite. This selfsustained process leads to autoamplification of secondary singlet oxygen generation and catalase inactivation. Inactivation of catalase allows the influx of H2O2 through aquaporins, leading to intracellular glutathione depletion and sensitization of the cells for apoptosis induction through lipid peroxidation. It also allows to establish intercellular apoptosis-inducing HOCl signaling, driven by active NOX1 and finalized by lipid peroxidation through hydroxyl radicals that activates the mitochondrial pathway of apoptosis. This experimentally established model is based on a triggering function of CAP and PAM-derived H2O2/nitrite that causes selective cell death in tumor cells based on their own ROS and RNS. This model explains the selectivity of CAP and PAM action towards tumor cells and is in contradiction to previous models that implicated that ROS/RNS from CAP or PAM were sufficient to directly cause cell death of tumor cells.

SUBMITTER: Bauer G

PROVIDER: S-EPMC6831866 | biostudies-other | 2019 Sep

REPOSITORIES: biostudies-other

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The synergistic effect between hydrogen peroxide and nitrite, two long-lived molecular species from cold atmospheric plasma, triggers tumor cells to induce their own cell death.

Bauer Georg G

Redox biology 20190808

Nitrite and H2O2 are long-lived species in cold atmospheric plasma and plasma-activated medium. It is known that their synergistic interaction is required for selective apoptosis induction in tumor cells that are treated with plasma-activated medium. This study shows that the interaction between nitrite and H2O2 leads to the formation of peroxynitrite, followed by singlet oxygen generation through the interaction between peroxynitrite and residual H<su ...[more]

PMID: 31421409

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Project description:Cold Atmospheric Plasma (CAP) is a promising novel method for biofilm inactivation as log-reduction values up to 4.0 log10 (CFU/cm2) have been reported. Nevertheless, as the efficacy of CAP itself is not sufficient for complete inactivation of mature biofilms, the hurdle technology could be applied in order to obtain higher combined efficacies. In this study, CAP treatment was combined with a mild hydrogen peroxide (H2O2) treatment for disinfection of 1 and 7 day(s) old Listeria monocytogenes and Salmonella Typhimurium biofilms. Three different treatment sequences were investigated in order to determine the most effective treatment sequence, i.e., (i) first CAP, then H2O2, (ii) first H2O2, then CAP, and (iii) a simultaneous treatment of CAP and H2O2. Removal of the biofilm, induction of sub-lethal injury, and H2O2 breakdown due to the presence of catalase within the biofilms were investigated in order to comment on their possible contribution to the combined inactivation efficacy. Results indicated that the preferred treatment sequence was dependent on the biofilm forming species, biofilm age, and applied H2O2 concentration [0.05 or 0.20% (v/v)]. At the lowest H2O2 concentration, the highest log-reductions were generally observed if the CAP treatment was preceded by the H2O2 treatment, while at the highest H2O2 concentration, the opposite sequence (first CAP, then H2O2) proved to be more effective. Induction of sub-lethal injury contributed to the combined bactericidal effect, while the presence of catalase within the biofilms resulted in an increased resistance. In addition, high log-reductions were partially the result of biofilm removal. The highest overall log-reductions [i.e., up to 5.42 ± 0.33 log10 (CFU/cm2)] were obtained at the highest H2O2 concentration if CAP treatment was followed by H2O2 treatment. As this resulted in almost complete inactivation of the L. monocytogenes and S. Typhimurium biofilms, the combined treatment of CAP and H2O2 proved to be a promising method for disinfection of abiotic surfaces.

Dataset Information

The synergistic effect between hydrogen peroxide and nitrite, two long-lived molecular species from cold atmospheric plasma, triggers tumor cells to induce their own cell death.

Publications

The synergistic effect between hydrogen peroxide and nitrite, two long-lived molecular species from cold atmospheric plasma, triggers tumor cells to induce their own cell death.

Similar Datasets

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