Skip to main content
SpringerLink
Log in

Mechanisms of a novel anticancer therapeutic strategy involving atmospheric pressure plasma-mediated apoptosis and DNA strand break formation

  • Review
  • Published:
Archives of Pharmacal Research Aims and scope Submit manuscript

Abstract

Atmospheric pressure plasma has been developed for a variety of biomedical applications due to its chemically reactive components. Recently, the plasma has emerged as a promising novel cancer therapy based on its ability to selectively ablate cancer cells while leaving normal cells essentially unaffected. The therapeutic effect of plasma is attributed to intracellular generation of reactive oxygen/nitrogen species (ROS/RNS) leading to mitochondria-mediated apoptosis and to activation of the DNA damage checkpoint signaling pathway via severe DNA strand break formation. However, the biochemical mechanisms responsible for appropriate activation of these physiological events and which pathway is more crucial for plasma-mediated cytotoxicity have not been clarified. Understanding the molecular link between ROS/RNS-mediated apoptosis and DNA damage-involved chromosome instability is critical for the development of more efficacious therapeutic strategies for selective killing of diverse cancer cells.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  • Ahn, H.J., K.I. Kim, G. Kim, E. Moon, S.S. Yang, and J.S. Lee. 2011. Atmospheric-pressure plasma jet induces apoptosis involving mitochondria via generation of free radicals. PLoS One 6: e28154.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Ahn, H.J., K.I. Kim, N.N. Hoan, C.H. Kim, E. Moon, K.S. Choi, S.S. Yang, and J.S. Lee. 2014. Targeting cancer cells with reactive oxygen and nitrogen species generated by atmospheric-pressure air plasma. PLoS One 9: e86173.

    Article  PubMed  PubMed Central  Google Scholar 

  • Alkawareek, M.Y., S.P. Gorman, W.G. Graham, and B.F. Gilmore. 2014. Potential cellular targets and antibacterial efficacy of atmospheric pressure non-thermal plasma. International Journal of Antimicrobial Agents 43: 154–160.

    Article  PubMed  CAS  Google Scholar 

  • Arjunan, K.P., V.K. Sharma, and S. Ptasinska. 2015. Effects of atmospheric pressure plasmas on isolated and cellular DNA-a review. International Journal of Molecular Sciences 16: 2971–3016.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Baik, K.Y., Y.H. Kim, Y.H. Ryu, H.S. Kwon, G. Park, H.S. Uhm, and E.H. Choi. 2013. Feeding-gas effects of plasma jets on Escherichia coli in physiological solutions. Plasma Processes and Polymers 10: 235–242.

    Article  CAS  Google Scholar 

  • Barnouin, K., M.L. Dubuisson, E.S. Child, S. Fernandez de Mattos, J. Glassford, R.H. Medema, D.J. Mann, and E.W. Lam. 2002. H2O2 induces a transient multi-phase cell cycle arrest in mouse fibroblasts through modulating cyclin D and p21Cip1 expression. Journal of Biological Chemistry 277: 13761–13770.

    Article  PubMed  CAS  Google Scholar 

  • Boudaiffa, B., P. Cloutier, D. Hunting, M.A. Huels, and L. Sanche. 2000. Resonant formation of DNA strand breaks by low-energy (3–20 eV) electrons. Science 287: 1658–1660.

    Article  PubMed  CAS  Google Scholar 

  • Chen, C.C., R.D. Kennedy, S. Sidi, A.T. Look, and A. D’Andrea. 2009. CHK1 inhibition as a strategy for targeting Fanconi anemia (FA) DNA repair pathway deficient tumors. Molecular Cancer 8: 24.

    Article  PubMed  PubMed Central  Google Scholar 

  • deRojas-Walker, T., S. Tamir, H. Ji, J.S. Wishnok, and S.R. Tannenbaum. 1995. Nitric oxide induces oxidative damage in addition to deamination in macrophage DNA. Chemical Research in Toxicology 8: 473–477.

    Article  PubMed  CAS  Google Scholar 

  • Dizdaroglu, M. 1991. Chemical determination of free radical-induced damage to DNA. Free Radical Biology and Medicine 10: 225–242.

    Article  PubMed  CAS  Google Scholar 

  • Dröge, W. 2002. Free radicals in the physiological control of cell function. Physiological Reviews 82: 47–95.

    Article  PubMed  Google Scholar 

  • Farmer, H., N. McCabe, C.J. Lord, A.N. Tutt, D.A. Johnson, T.B. Richardson, M. Santarosa, K.J. Dillon, I. Hickson, C. Knights, N.M. Martin, S.P. Jackson, G.C. Smith, and A. Ashworth. 2005. Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature 434: 917–921.

    Article  PubMed  CAS  Google Scholar 

  • Fridman, G., M. Peddinghaus, H. Ayan, A. Fridman, M. Balasubramanian, A. Gutsol, A. Brooks, and G. Friedman. 2006. Blood coagulation and living tissue sterilization by floating electrode dielectric barrier discharge in air. Plasma Chemistry and Plasma Processing 26: 425–442.

    Article  CAS  Google Scholar 

  • Fridman, G., A. Shereshevsky, M.M. Jost, A.D. Brooks, A. Fridman, A. Gutsol, V. Vasilets, and G. Friedman. 2007. Floating electrode dielectric barrier discharge plasma in air promoting apoptotic behavior in melanoma skin cancer cell lines. Plasma Chemistry and Plasma Processing 27: 163–176.

    Article  CAS  Google Scholar 

  • Georgescu, N., and A. Lupu. 2010. Tumoral and normal cells treatment with high-voltage pulsed cold atmospheric plasma jets. IEEE Transactions on Plasma Science 38: 1949–1956.

    Article  Google Scholar 

  • Görsdorf, S., K.E. Appel, C. Engeholm, and G. Obe. 1990. Nitrogen dioxide induces DNA single-strand breaks in cultured Chinese hamster cells. Carcinogenesis 11: 37–41.

    Article  PubMed  Google Scholar 

  • Graves, D.B. 2012. The emerging role of reactive oxygen and nitrogen species in redox biology and some implications for plasma applications to medicine and biology. Journal of Physics D 45: 263001.

    Article  Google Scholar 

  • Halliwell, B., and O.I. Aruoma. 1991. DNA damage by oxygen-derived species: Its mechanism and measurement in mammalian systems. FEBS Letters 281: 9–19.

    Article  PubMed  CAS  Google Scholar 

  • Han, X., W.A. Cantrell, E.E. Escobar, and S. Ptasinska. 2014. Plasmid DNA damage induced by helium atmospheric pressure plasma jet. European Physical Journal D: Atomic, Molecular and Optical Physics 68: 46.

    Article  Google Scholar 

  • Ira, G., A. Pellicioli, A. Balijja, X. Wang, S. Fiorani, W. Carotenuto, G. Liberi, D. Bressan, L. Wan, N.M. Hollingsworth, J.E. Haber, and M. Foiani. 2004. DNA end resection, homologous recombination and DNA damage checkpoint activation require CDK1. Nature 431: 1011–1017.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Iseki, S., K. Nakamura, M. Hayashi, H. Tanaka, H. Kondo, H. Kajiyama, H. Kano, F. Kikkawa, and M. Hori. 2012. Selective killing of ovarian cancer cells through induction of apoptosis by nonequilibrium atmospheric pressure plasma. Applied Physics Letters 100: 113702.

    Article  Google Scholar 

  • Ito, K., S. Inoue, Y. Hikaru, and S. Kawanishi. 2005. Mechanism of site-specific DNA damage induced by ozone. Mutation Research 585: 60–70.

    Article  PubMed  CAS  Google Scholar 

  • Kaelin Jr, W.G. 2005. The concept of synthetic lethality in the context of anticancer therapy. Nature Reviews Cancer 5: 689–698.

    Article  PubMed  CAS  Google Scholar 

  • Kalghatgi, S., C.M. Kelly, E. Cerchar, B. Torabi, O. Alekseev, A. Fridman, G. Friedman, and J. Azizkhan-Clifford. 2011. Effects of non-thermal plasma on mammalian cells. PLoS One 6: e16270.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Keidar, M., R. Walk, A. Shashurin, P. Srinivasan, A. Sandler, S. Dasgupta, R. Ravi, R. Guerrero-Preston, and B. Trink. 2011. Cold plasma selectivity and the possibility of a paradigm shift in cancer therapy. British Journal of Cancer 105: 1295–1301.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Kennedy, R.D., C.C. Chen, P. Stuckert, E.M. Archila, M.A. De la Vega, L.A. Moreau, A. Shimamura, and A.D. D’Andrea. 2007. Fanconi anemia pathway-deficient tumor cells are hypersensitive to inhibition of ataxia telangiectasia mutated. Journal of Clinical Investigation 117: 1440–1449.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Kim, C.H., J.H. Bahn, S.H. Lee, G.Y. Kim, S.I. Jun, K. Lee, and S.J. Baek. 2010a. Induction of cell growth arrest by atmospheric non-thermal plasma in colorectal cancer cells. Journal of Biotechnology 150: 530–538.

    Article  PubMed  CAS  Google Scholar 

  • Kim, G.J., W. Kim, K.T. Kim, and J.K. Lee. 2010b. DNA damage and mitochondria dysfunction in cell apoptosis induced by nonthermal air plasma. Applied Physics Letters 96: 021502.

    Article  Google Scholar 

  • Kim, K., J.D. Choi, Y.C. Hong, G. Kim, E.J. Noh, J.S. Lee, and S.S. Yang. 2011. Atmospheric-pressure plasma-jet from micronozzle array and its biological effects on living cells for cancer therapy. Applied Physics Letters 98: 073701.

    Article  Google Scholar 

  • Kirchner, J.J., S.T. Sigurdson, and P.B. Hopkins. 1992. Interstrand cross-linking of duplex DNA by nitrous acid: covalent structure of the dG-to-dG cross-link at the sequence 5’-CG. Journal of the American Chemical Society 114: 4021–4027.

    Article  CAS  Google Scholar 

  • Kong, M.G., G. Kroesen, G.E. Morfill, T. Nosenko, T. Shimizu, J. van Dijk, and J.L. Zimmermann. 2009. Plasma medicine: an introductory review. New Journal of Physics 11: 115012.

    Article  Google Scholar 

  • Kryston, T.B., A.B. Georgiev, P. Pissis, and A.G. Georgakilas. 2011. Role of oxidative stress and DNA damage in human carcinogenesis. Mutation Research 711: 193–201.

    Article  PubMed  CAS  Google Scholar 

  • Leduc, M., D. Guay, R.L. Leask, and S. Coulombe. 2009. Cell permeabilization using a non-thermal plasma. New Journal of Physics 11: 115021.

    Article  Google Scholar 

  • Leduc, M., D. Guay, S. Coulombe, and R.L. Leask. 2010. Effects of non-thermal plasmas on DNA and mammalian cells. Plasma Process Polym 7: 899–909.

    Article  CAS  Google Scholar 

  • Lee, Y., K. Kim, K.T. Kang, J.S. Lee, S.S. Yang, and W.H. Chung. 2014. Atmospheric-pressure plasma jet induces DNA double-strand breaks that require a Rad51-mediated homologous recombination for repair in Saccharomyces cerevisiae. Archives of Biochemistry and Biophysics 560: 1–9.

    Article  PubMed  CAS  Google Scholar 

  • Lengauer, C., K.W. Kinzler, and B. Vogelstein. 1998. Genetic instabilities in human cancers. Nature 396: 643–649.

    Article  PubMed  CAS  Google Scholar 

  • Li, G., H.P. Li, L.Y. Wang, S. Wang, H.Z. Zhao, W.T. Sun, X.H. Xing, and C.Y. Bao. 2008. Genetic effects of radio-frequency, atmospheric-pressure glow discharges with helium. Applied Physics Letters 92: 221504.

    Article  Google Scholar 

  • Ma, R.N., H.Q. Feng, Y.D. Liang, G. Zhang, Y. Tian, B. Su, J. Zhang, and J. Fang. 2013. An atmospheric-pressure cold plasma leads to apoptosis in Saccharomyces cerevisiae by accumulating intracellular reactive oxygen species and calcium. Journal of Physics D 46: 285401.

    Article  Google Scholar 

  • Ma, Y., C.S. Ha, S.W. Hwang, H.J. Lee, G.C. Kim, K. Lee, and K. Song. 2014. Non-thermal atmospheric pressure plasma preferentially induces apoptosis in p53-mutated cancer cells by activating ROS stress-response pathways. PLoS One 9: e91947.

    Article  PubMed  PubMed Central  Google Scholar 

  • McCabe, N., N.C. Turner, C.J. Lord, K. Kluzek, A. Bialkowska, S. Swift, S. Giavara, M.J. O’Connor, A.N. Tutt, M.Z. Zdzienicka, G.C. Smith, and A. Ashworth. 2006. Deficiency in the repair of DNA damage by homologous recombination and sensitivity to poly(ADP-ribose) polymerase inhibition. Cancer Research 66: 8109–8115.

    Article  PubMed  CAS  Google Scholar 

  • McLornan, D.P., A. List, and G.J. Mufti. 2014. Applying synthetic lethality for the selective targeting of cancer. New England Journal of Medicine 371: 1725–1735.

    Article  PubMed  CAS  Google Scholar 

  • McManus, K.J., I.J. Barrett, Y. Nouhi, and P. Hieter. 2009. Specific synthetic lethal killing of RAD54B-deficient human colorectal cancer cells by FEN1 silencing. Proceedings of the National Academy of Sciences of the United States of America 106: 3276–3281.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Moreau, M., N. Orange, and M.G.J. Feuilloley. 2008. Non-thermal plasma technologies: New tools for biodecontamination. Biotechnology Advances 26: 610–617.

    Article  PubMed  CAS  Google Scholar 

  • Oberhammer, F., J.W. Wilson, C. Dive, I.D. Morris, J.A. Hickman, A.E. Wakeling, P.R. Walker, and M. Sikorska. 1993. Apoptotic death in epithelial cells: cleavage of DNA to 300 and/or 50 kb fragments prior to or in the absence of internucleosomal fragmentation. EMBO Journal 12: 3679–3684.

    PubMed  CAS  PubMed Central  Google Scholar 

  • O’Connell, D., L.J. Cox, W.B. Hyland, S.J. McMahon, S. Reuter, W.G. Graham, T. Gans, and F.J. Currell. 2011. Cold atmospheric pressure plasma jet interactions with plasmid DNA. Applied Physics Letters 98: 043701.

    Article  Google Scholar 

  • Panngom, K., K.Y. Baik, M.K. Nam, J.H. Han, H. Rhim, and E.H. Choi. 2013. Preferential killing of human lung cancer cell lines with mitochondrial dysfunction by nonthermal dielectric barrier discharge plasma. Cell Death and Disease 4: e642.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Pelicano, H., D. Carney, and P. Huang. 2004. ROS stress in cancer cells and therapeutic implications. Drug Resistance Updates 7: 97–110.

    Article  PubMed  CAS  Google Scholar 

  • Pogozelski, W.K., and T.D. Tullius. 1998. Oxidative strand scission of nucleic acids: routes initiated by hydrogen abstraction from the sugar moiety. Chemical Reviews 98: 1089–1108.

    Article  PubMed  CAS  Google Scholar 

  • Ptasinska, S., B. Bahnev, A. Stypczynska, M. Bowden, N.J. Mason, and N.S.J. Braithwaite. 2010. DNA strand scission induced by a non-thermal atmospheric pressue plasma jet. Physical Chemistry Chemical Physics: PCCP 12: 7779–7781.

    Article  PubMed  CAS  Google Scholar 

  • Rogakou, E.P., D.R. Pilch, A.H. Orr, V.S. Ivanova, and W.M. Bonner. 1998. DNA double-stranded breaks induce histone H2AX phosphorylation on serine 139. Journal of Biological Chemistry 273: 5858–5868.

    Article  PubMed  CAS  Google Scholar 

  • Rupf, S., A. Lehmann, M. Hannig, B. Schäfer, A. Schubert, U. Feldmann, and A. Schindler. 2010. Killing of adherent oral microbes by a non-thermal atmospheric plasma jet. Journal of Medical Microbiology 59: 206–212.

    Article  PubMed  Google Scholar 

  • Sage, E., and L. Harrison. 2011. Clustered DNA lesion repair in eukaryotes: relevance to mutagenesis and cell survival. Mutation Research 711: 123–133.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Sajesh, B.V., M. Bailey, Z. Lichtensztejn, P. Hieter, and K.J. McManus. 2013. Synthetic lethal targeting of superoxide dismutase 1 selectively kills RAD54B-deficient colorectal cancer cells. Genetics 195: 757–767.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Sies, H., and C.F. Menck. 1992. Singlet oxygen induced DNA damage. Mutation Research 275: 367–375.

    Article  PubMed  CAS  Google Scholar 

  • Sultana, R., D.R. McNeill, R. Abbotts, M.Z. Mohammed, M.Z. Zdzienicka, H. Qutob, C. Seedhouse, C.A. Laughton, P.M. Fischer, P.M. Patel 3rd, D.M. Wilson, and S. Madhusudan. 2012. Synthetic lethal targeting of DNA double-strand break repair deficient cells by human apurinic/apyrimidinic endonuclease inhibitors. International Journal of Cancer 131: 2433–2444.

    Article  CAS  Google Scholar 

  • Szabó, C., and H. Ohshima. 1997. DNA damage induced by peroxynitrite: subsequent biological effects. Nitric Oxide 1: 373–385.

    Article  PubMed  Google Scholar 

  • Vandamme, M., E. Robert, S. Lerondel, V. Sarron, D. Ries, S. Dozias, J. Sobilo, D. Gosset, C. Kieda, B. Legrain, J.M. Pouvesle, and A.L. Pape. 2012. ROS implication in a new antitumor strategy based on non-thermal plasma. International Journal of Cancer 130: 2185–2194.

    Article  CAS  Google Scholar 

  • Volotskova, O., T.S. Hawley, M.A. Stepp, and M. Keidar. 2012. Targeting the cancer cell cycle by cold atmospheric plasma. Scientific Reports 2: 636.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Wang, M., B. Holmes, X. Cheng, W. Zhu, M. Keidar, and L.G. Zhang. 2013. Cold atmospheric plasma for selectively ablating metastatic breast cancer cells. PLoS One 8: e73741.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Ward, J.F., W.F. Blakely, and E.I. Joner. 1985. Mammalian cells are not killed by DNA single-strand breaks caused by hydroxyl radicals from hydrogen peroxide. Radiation Research 103: 383–392.

    Article  PubMed  CAS  Google Scholar 

  • Wende, K., S. Straßenburg, B. Haertel, M. Harms, S. Holtz, A. Barton, K. Masur, T. von Woedtke, and U. Lindequist. 2014. Atmospheric pressure plasma jet treatment evokes transient oxidative stress in HaCaT keratinocytes and influences cell physiology. Cell Biology International 38: 412–425.

    Article  PubMed  CAS  Google Scholar 

  • Yang, J., Y. Yu, H.E. Hamrick, and P.J. Duerksen-Hughes. 2003. ATM, ATR and DNA-PK: initiators of the cellular genotoxic stress responses. Carcinogenesis 24: 1571–1580.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This research was supported by the Duksung Women’s University Research Grants 2014.

Author information

Authors and Affiliations

  1. College of Pharmacy, Duksung Women’s University, 33, Samyangro 144-gil, Dobong-gu, Seoul, 132-714, Korea

    Woo-Hyun Chung

  2. Innovative Drug Center, Duksung Women’s University, Seoul, 132-714, Korea

    Woo-Hyun Chung

Authors
  1. Woo-Hyun Chung
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Woo-Hyun Chung.

Ethics declarations

Conflict of interest

The author declares that he has no conflict of interests.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Chung, WH. Mechanisms of a novel anticancer therapeutic strategy involving atmospheric pressure plasma-mediated apoptosis and DNA strand break formation. Arch. Pharm. Res. 39, 1–9 (2016). https://doi.org/10.1007/s12272-015-0644-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12272-015-0644-1

Keywords

Search

Navigation