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Plasma Medicine
SJR: 0.271 SNIP: 0.316 CiteScore™: 1.9

ISSN Imprimir: 1947-5764
ISSN En Línea: 1947-5772

Plasma Medicine

DOI: 10.1615/PlasmaMed.2018028781
pages 335-343

Universality of Micromolar-Level Cell-Based Hydrogen Peroxide Generation during Direct Cold Atmospheric Plasma Treatment

Dayun Yan
Department of Mechanical and Aerospace Engineering, The George Washington University, Science and Engineering Hall, 800 22nd Street, NW, Room 3550, Washington, DC 20052, USA
Li Lin
Department of Pathology, The Second Affiliated Hospital of Nanjing Medical University, 121 Jiangjiayuan Rd, Nanjing 010011, China; Department of Mechanical and Aerospace Engineering, The George Washington University, Washington, DC 20052, USA
Wenjun Xu
State Key Laboratory of Electrical Insulation and Power Equipment, Xi'an Jiaotong University, Xi'an, 710049, China
Niku Nourmohammadi
School of Medicine and Health Sciences, The George Washington University, Washington, D.C. 20037
Jonathan H. Sherman
Neurological Surgery, The George Washington University, Foggy Bottom South Pavilion, 22nd Street NW, 7th Floor, Washington, DC 20052, USA
Michael Keidar
Department of Mechanical and Aerospace Engineering, The George Washington University, Science and Engineering Hall, 800 22nd Street, NW, Room 3550, Washington, DC 20052, USA


Understanding the interaction between cold atmospheric plasma (CAP) and cells is a critical challenge in plasma medicine. CAP has shown promising application for cancer treatment. To date, dozens of cancer cells have been selectively killed during in vitro studies, and CAP-originated reactive species have been regarded to be the primary factor causing cancer cell death. In the past, we investigated hydrogen peroxide (H2O2) generation at the micromolar level using two CAP-treated cancer cell lines. In this study, we further demonstrate the universality of such strong cell-based H2O2 generation in eight cancer cell lines. Nearly all lines showed capacity to generate a micromolar level of H2O2 during 1 min of CAP treatment when discharge voltage (peak value) was > 3.30 kV. Generally, higher discharge voltage corresponds to stronger cell-based H2O2 generation, although some cell lines produce maximum H2O2 generation at relatively low discharge voltage. Cell-based H2O2 generation may involve interaction between cancer cells and reactive oxygen species in CAP. The CAP optical emission spectrum demonstrates a significant increase in singlet oxygen (O) and hydroxyl (OH) radicals in CAP when discharge voltage is > 3.30 kV. This study demonstrates the universality of cell-based H2O2 generation that has not been considered in previous studies.


  1. Keidar M. A prospectus on innovations in the plasma treatment of cancer. Phys Plasmas. 2018;25(8):083504.

  2. Keidar M, Yan D, Beilis I, Trink B, Sherman J. Plasmas for treating cancer: Opportunities for adaptive and self-adaptive approaches. Trends Biotechnol. 2018;36(6):586-93.

  3. Laroussi M. Low-temperature plasma jet for biomedical applications: A review. IEEE Trans Plasma Sci. 2015;43(3):703-12.

  4. Fridman G, Friedman G, Gutsol A, Shekhter A, Vasilets V, Fridman A. Applied plasma medicine. Plasma Proc Polym. 2008;5(6):503-33.

  5. Graves D. The emerging role of reactive oxygen and nitrogen species in redox biology and some implications for plasma applications to medicine and biology. J Phys D Appl Phys. 2012;45:263001-42.

  6. Yan D, Sherman J, Keidar M. Cold atmospheric plasma, a novel promising anti-cancer treatment modality. Oncotarget. 2017;8(9):15977.

  7. Keidar M, Shashurin A, Volotskova O, Ann M, Srinivasan P, Sandler A, Trink B. Cold atmospheric plasma in cancer therapy. Phys Plasmas. 2013;20(5):057101.

  8. Ishaq M, Evans M, Ostrikov K. Effect of atmospheric gas plasmas on cancer cell signaling. Int J Cancer. 2014;134(7):1517-28.

  9. Yan D, Talbot A, Nourmohammadi N, Sherman J, Cheng X, Keidar M. Toward understanding the selective anticancer capacity of cold atmospheric plasma: A model based on aquaporins. Biointer-phases. 2015;10(4):40801.

  10. Yan D, Cui H, Zhu W, Talbot A, Zhang L, Sherman J, Keidar M. The strong cell-based hydrogen peroxide generation triggered by cold atmospheric plasma. Sci Rep. 2017;7(1):10831.

  11. Shashurin A, Stepp M, Hawley T, Pal-Ghosh S, Brieda L, Bronnikov S, Jurjus R, Keidar M. Influence of cold plasma atmospheric jet on surface integrin expression of living cells. Plasma Proc Polym. 2010;7(3-4):294-300.

  12. Yan D, Talbot A, Nourmohammadi N, Cheng X, Canady J, Sherman J, Keidar M. Principles of using cold atmospheric plasma stimulated media for cancer treatment. Sci Rep. 2015;5:18339.

  13. Yan D, Cui H, Zhu W, Nourmohammadi N, Milberg J, Zhang L, Sherman J, Keidar M. The specific vulnerabilities of cancer cells to the cold atmospheric plasma-stimulated solutions. Sci Rep. 2017;7(1):4479.

  14. Kalghatgi S, Kelly CM, Cerchar E, Torabi B, Alekseev O, Fridman A, Friedman G, Azizkhan-Clifford J. Effects ofnon-thermal plasma on mammalian cells. PLoS ONE. 2011;6(l):el6270.

  15. Nozik-Grayck E, Suliman H, Piantadosi C. Extracellular superoxide dismutase. Int J Biochem Cell Biol. 2005;37(12):2466-71.

  16. Ameziane-El-Hassani R, Schlumberger M, Dupuy C. NADPH oxidases: New actors in thyroid cancer? Nat Rev Endocrinol. 2016;12(8):485-94.

  17. Veal E, Day A, Morgan B. Hydrogen peroxide sensing and signaling. Mol Cell. 2007;26(1):1-14.

  18. Sakiyama Y, Graves D, Chang H, Shimizu T, Morfill G. Plasma chemistry model of surface microdis-charge in humid air and dynamics of reactive neutral species. J Phys D Appl Phys. 2012;45(42):425201.

  19. Kossyi IA, Yu Kostinsky A, Matveyev AA, Silakov VP. Kinetic scheme of the non-equlibrium discharge jn nitrogen-oxygen mixtures. Plasma Sources Sci Technol. 1992;1(3):207-20.

  20. Golubovskii YB, Maiorov V, Behnke J, Behnke JF. Modelling of the homogeneous barrier discharge in helium at atmospheric pressure. J Phys D Appl Phys. 2003;36(1):39-49.

  21. Norberg S, Johnsen E, Kushner M. Formation of reactive oxygen and nitrogen species by repetitive negatively pulsed helium atmospheric pressure plasma jets propagating into humid air. Plasma Sources Sci Technol. 2015;24(3):35026.

  22. Hagelaar G, Pitchford L. Solving the Boltzmann equation to obtain electron transport coefficients and rate coefficients for fluid models. Plasma Sources Sci Technol. 2005;14(4):722-33.

  23. Lu X, Naidis G, Laroussi M, Ostrikov K. Guided ionization waves theory and experiments. Phys Rep. 2018;540(3):123-66.

  24. Szatrowski T, Nathan C. Production of large amounts of hydrogen peroxide by human tumor cells. Cancer Res. 1991;51(3):794-9.

  25. Schmielau J, Finn O. Activated granulocytes and granulocyte-derived hydrogen peroxide are the underlying mechanism of suppression of T-cell function in advanced cancer patients. Cancer Res. 2001;61(12):4756-60.

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