You're using an outdated browser. Please upgrade to a modern browser for the best experience.
Plasma-Treated Solutions in Cancer Therapy: Comparison
View Latest Version
Please note this is a comparison between Version 2 by Conner Chen and Version 1 by Mounir Laroussi.

Cold physical plasma is a partially ionized gas generating various reactive oxygen and nitrogen species (ROS/RNS) simultaneously. ROS/RNS have therapeutic effects when applied to cells and tissues either directly from the plasma or via exposure to solutions that have been treated beforehand using plasma processes. This review addresses the challenges and opportunities of plasma-treated solutions (PTSs) for cancer treatment. These PTSs include plasma-treated cell culture media in experimental research as well as clinically approved solutions such as saline and Ringer’s lactate, which, in principle, already qualify for testing in therapeutic settings. Several types of cancers were found to succumb to the toxic action of PTSs, suggesting a broad mechanism of action based on the tumor-toxic activity of ROS/RNS stored in these solutions. Moreover, it is indicated that the PTS has immuno-stimulatory properties. Two different routes of application are currently envisaged in the clinical setting. One is direct injection into the bulk tumor, and the other is lavage in patients suffering from peritoneal carcinomatosis adjuvant to standard chemotherapy. While many promising results have been achieved so far, several obstacles, such as the standardized generation of large volumes of sterile PTS, remain to be addressed.

  • cold physical plasma
  • low-temperature plasma
  • PTS
Please wait, diff process is still running!

References

  1. Tanaka, H.; Mizuno, M.; Ishikawa, K.; Takeda, K.; Nakamura, K.; Utsumi, F.; Kajiyama, H.; Kano, H.; Okazaki, Y.; Toyokuni, S.; et al. Plasma medical science for cancer therapy: Toward cancer therapy using Nonthermal Atmospheric Pressure Plasma. IEEE Trans. Plasma Sci. 2014, 42, 3760–3764.
  2. Yan, D.; Sherman, J.H.; Keidar, M. The application of the cold atmospheric plasma-activated solutions in cancer treatment. Anti-Cancer Agents Med. Chem. 2018, 18, 769–775.
  3. Yan, D.; Nourmohammadi, N.; Bian, K.; Murad, F.; Sherman, J.H.; Keidar, M. Stabilizing the cold plasma-stimulated medium by regulating medium’s composition. Sci. Rep. 2016, 6, 26016.
  4. Sato, Y.; Yamada, S.; Takeda, S.; Hattori, N.; Nakamura, K.; Tanaka, H.; Mizuno, M.; Hori, M.; Kodera, Y. Effect of plasma-activated lactated ringer’s solution on pancreatic cancer cells in vitro and in vivo. Ann. Surg. Oncol. 2017, 25, 299–307.
  5. Verlackt, C.C.W.; Van Boxem, W.; Bogaerts, A. Transport and accumulation of plasma generated species in aqueous solution. Phys. Chem. Chem. Phys. 2018, 20, 6845–6859.
  6. Freund, E.; Bekeschus, S. Gas plasma-oxidized liquids for cancer treatment: Pre-clinical relevance, immuno-oncology, and clinical obstacles. IEEE Trans. Radiat. Plasma Med. Sci. 2020, 1.
  7. Bekeschus, S.; Freund, E.; Wende, K.; Gandhirajan, R.K.; Schmidt, A. Hmox1 Upregulation Is a Mutual Marker in Human Tumor Cells Exposed to Physical Plasma-Derived Oxidants. Antioxidants 2018, 7, 151.
  8. Xu, D.; Cui, Q.; Xu, Y.; Wang, B.; Tian, M.; Li, Q.; Liu, Z.; Liu, D.; Chen, H.; Kong, M.G. Systemic study on the safety of immuno-deficient nude mice treated by atmospheric plasma-activated water. Plasma Sci. Technol. 2018, 20, 044003.
  9. Tanaka, H.; Nakamura, K.; Mizuno, M.; Ishikawa, K.; Takeda, K.; Kajiyama, H.; Utsumi, F.; Kikkawa, F.; Hori, M. Non-thermal atmospheric pressure plasma activates lactate in Ringer’s solution for anti-tumor effects. Sci. Rep. 2016, 6, 36282.
  10. Freund, E.; Liedtke, K.R.; Gebbe, R.; Heidecke, A.K.; Partecke, L.-I.; Bekeschus, S. In Vitro Anticancer Efficacy of Six Different Clinically Approved Types of Liquids Exposed to Physical Plasma. IEEE Trans. Radiat. Plasma Med Sci. 2019, 3, 588–596.
  11. Wende, K.; Reuter, S.; Von Woedtke, T.; Weltmann, K.-D.; Masur, K. Redox-Based Assay for Assessment of Biological Impact of Plasma Treatment. Plasma Process. Polym. 2014, 11, 655–663.
  12. Tanaka, H.; Mizuno, M.; Ishikawa, K.; Nakamura, K.; Kajiyama, H.; Kano, H.; Kikkawa, F.; Hori, M. Plasma-Activated Medium Selectively Kills Glioblastoma Brain Tumor Cells by Down-Regulating a Survival Signaling Molecule, AKT Kinase. Plasma Med. 2011, 1, 265–277.
  13. Utsumi, F.; Kajiyama, H.; Nakamura, K.; Tanaka, H.; Mizuno, M.; Ishikawa, K.; Kondo, H.; Kano, H.; Hori, M.; Kikkawa, F. Effect of Indirect Nonequilibrium Atmospheric Pressure Plasma on Anti-Proliferative Activity against Chronic Chemo-Resistant Ovarian Cancer Cells In Vitro and In Vivo. PLoS ONE 2013, 8, e81576.
  14. Freund, E.; Liedtke, K.R.; Van Der Linde, J.; Metelmann, H.-R.; Heidecke, C.-D.; Partecke, L.-I.; Bekeschus, S. Physical plasma-treated saline promotes an immunogenic phenotype in CT26 colon cancer cells in vitro and in vivo. Sci. Rep. 2019, 9, 1–18.
  15. Adachi, T.; Tanaka, H.; Nonomura, S.; Hara, H.; Kondo, S.-I.; Hori, M. Plasma-activated medium induces A549 cell injury via a spiral apoptotic cascade involving the mitochondrial–nuclear network. Free Radic. Biol. Med. 2015, 79, 28–44.
  16. Wende, K.; Bekeschus, S.; Schmidt, A.; Jatsch, L.; Hasse, S.; Weltmann, K.D.; Masur, K.; von Woedtke, T. Risk assessment of a cold argon plasma jet in respect to its mutagenicity. Mutat. Res. Genet. Toxicol Environ. Mutagen 2016, 798–799, 48–54.
  17. Torii, K.; Yamada, S.; Nakamura, K.; Tanaka, H.; Kajiyama, H.; Tanahashi, K.; Iwata, N.; Kanda, M.; Kobayashi, D.; Tanaka, C.; et al. Effectiveness of plasma treatment on gastric cancer cells. Gastric Cancer 2015, 18, 635–643.
  18. Hattori, N.; Yamada, S.; Torii, K.; Takeda, S.; Nakamura, K.; Tanaka, H.; Kajiyama, H.; Kanda, M.; Fujii, T.; Nakayama, G.; et al. Effectiveness of plasma treatment on pancreatic cancer cells. Int. J. Oncol. 2015, 47, 1655–1662.
  19. Bekeschus, S.; Käding, A.; Schröder, T.; Wende, K.; Hackbarth, C.; Liedtke, K.R.; Van Der Linde, J.; Von Woedtke, T.; Heidecke, C.-D.; Partecke, L.-I. Cold Physical Plasma-Treated Buffered Saline Solution as Effective Agent Against Pancreatic Cancer Cells. Anti-Cancer Agents Med. Chem. 2018, 18, 824–831.
  20. Liedtke, K.-R.; Freund, E.; Hermes, M.; Oswald, S.; Heidecke, C.-D.; Partecke, L.-I.; Bekeschus, S. Gas Plasma-Conditioned Ringer’s Lactate Enhances the Cytotoxic Activity of Cisplatin and Gemcitabine in Pancreatic Cancer In Vitro and In Ovo. Cancers 2020, 12, 123.
  21. Bundscherer, L.; Bekeschus, S.; Tresp, H.; Hasse, S.; Reuter, S.; Weltmann, K.-D.; Lindequist, U.; Masur, K. Viability of Human Blood Leukocytes Compared with Their Respective Cell Lines after Plasma Treatment. Plasma Med. 2013, 3, 71–80.
  22. Schmidt, A.; Rödder, K.; Hasse, S.; Masur, K.; Toups, L.; Lillig, C.H.; Von Woedtke, T.; Wende, K.; Bekeschus, S. Redox-regulation of activator protein 1 family members in blood cancer cell lines exposed to cold physical plasma-treated medium. Plasma Process. Polym. 2016, 13, 1179–1188.
  23. Schmidt, A.; Bekeschus, S.; Von Woedtke, T.; Hasse, S. Cell migration and adhesion of a human melanoma cell line is decreased by cold plasma treatment. Clin. Plasma Med. 2015, 3, 24–31.
  24. Mohades, S.; Barekzi, N.; Laroussi, M. Efficacy of Low Temperature Plasma against SCaBER Cancer Cells. Plasma Process. Polym. 2014, 11, 1150–1155.
  25. Tornin, J.; Mateu-Sanz, M.; Rodríguez, A.; Labay, C.; Rodríguez, R.; Canal, C. Pyruvate Plays a Main Role in the Antitumoral Selectivity of Cold Atmospheric Plasma in Osteosarcoma. Sci. Rep. 2019, 9, 1–13.
  26. Biscop, E.; Lin, A.; Van Boxem, W.; Van Loenhout, J.; De Backer, J.; Deben, C.; Dewilde, S.; Smits, E.; Bogaerts, A.A. Influence of Cell Type and Culture Medium on Determining Cancer Selectivity of Cold Atmospheric Plasma Treatment. Cancers 2019, 11, 1287.
  27. Reuter, S.; Von Woedtke, T.; Weltmann, K.-D. The kINPen—A review on physics and chemistry of the atmospheric pressure plasma jet and its applications. J. Phys. D Appl. Phys. 2018, 51, 233001.
  28. Wende, K.; von Woedtke, T.; Weltmann, K.D.; Bekeschus, S. Chemistry and biochemistry of cold physical plasma derived reactive species in liquids. Biol. Chem. 2018, 400, 19–38.
  29. Bekeschus, S.; Kolata, J.; Winterbourn, C.; Kramer, A.; Turner, R.; Weltmann, K.D.; Bröker, B.; Masur, K. Hydrogen peroxide: A central player in physical plasma-induced oxidative stress in human blood cells. Free Radic. Res. 2014, 48, 542–549.
  30. Bauer, G. Targeting Protective Catalase of Tumor Cells with Cold Atmospheric Plasma- Activated Medium (PAM). Anti-Cancer Agents Med. Chem. 2018, 18, 784–804.
  31. Bauer, G. 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. Redox Biol. 2019, 26, 101291.
  32. Kurake, N.; Tanaka, H.; Ishikawa, K.; Kondo, T.; Sekine, M.; Nakamura, K.; Kajiyama, H.; Kikkawa, F.; Mizuno, M.; Hori, M. Cell survival of glioblastoma grown in medium containing hydrogen peroxide and/or nitrite, or in plasma-activated medium. Arch. Biochem. Biophys. 2016, 605, 102–108.
  33. Bauer, G. Intercellular singlet oxygen-mediated bystander signaling triggered by long-lived species of cold atmospheric plasma and plasma-activated medium. Redox Biol. 2019, 26, 101301.
  34. Yan, D.; Cui, H.; Zhu, W.; Nourmohammadi, N.; Milberg, J.; Zhang, L.G.; Sherman, J.H.; Keidar, M. The specific vulnerabilities of cancer cells to the cold atmospheric plasma-stimulated solutions. Sci. Rep. 2017, 7, 4479.
  35. Kalghatgi, S.; Kelly, C.M.; Cerchar, E.; Torabi, B.; Alekseev, O.; Fridman, A.; Friedman, G.; Azizkhan-Clifford, J. Effects of Non-Thermal Plasma on Mammalian Cells. PLoS ONE 2011, 6, e16270.
  36. Furuta, R.; Kurake, N.; Ishikawa, K.; Takeda, K.; Hashizume, H.; Tanaka, H.; Kondo, H.; Sekine, M.; Hori, M. Intracellular responses to reactive oxygen and nitrogen species, and lipid peroxidation in apoptotic cells cultivated in plasma-activated medium. Plasma Process. Polym. 2017, 14, 1700123.
  37. Winterbourn, C.C. The challenges of using fluorescent probes to detect and quantify specific reactive oxygen species in living cells. Biochim. Biophys. Acta (BBA) Gen. Subj. 2014, 1840, 730–738.
  38. Kalyanaraman, B.; Darleyusmar, V.M.; Davies, K.J.A.; Dennery, P.A.; Forman, H.J.; Grisham, M.B.; Mann, G.E.; Moore, K.; Roberts, L.J.; Ischiropoulos, H. Measuring reactive oxygen and nitrogen species with fluorescent probes: Challenges and limitations. Free Radic. Biol. Med. 2012, 52, 1–6.
  39. Tanaka, H.; Mizuno, M.; Katsumata, Y.; Ishikawa, K.; Kondo, H.; Hashizume, H.; Okazaki, Y.; Toyokuni, S.; Nakamura, K.; Yoshikawa, N.; et al. Oxidative stress-dependent and -independent death of glioblastoma cells induced by non-thermal plasma-exposed solutions. Sci. Rep. 2019, 9, 13657.
  40. Bekeschus, S.; Wende, K.; Hefny, M.M.; Rödder, K.; Jablonowski, H.; Schmidt, A.; Von Woedtke, T.; Weltmann, K.-D.; Benedikt, J. Oxygen atoms are critical in rendering THP-1 leukaemia cells susceptible to cold physical plasma-induced apoptosis. Sci. Rep. 2017, 7, 2791.
  41. Bekeschus, S.; Wulf, C.P.; Freund, E.; Koensgen, D.; Mustea, A.; Weltmann, K.-D.; Stope, M.B. Plasma treatment of ovarian cancer cells mitigates their immuno-modulatory products active on THP-1 monocytes. Plasma 2018, 1, 201–217.
  42. Privat-Maldonado, A.; Gorbanev, Y.; Dewilde, S.; Smits, E.; Bogaerts, A. Reduction of human glioblastoma spheroids using cold atmospheric plasma: The combined effect of short- and long-lived reactive species. Cancers 2018, 10, 394.
  43. Masur, K.; Von Behr, M.; Bekeschus, S.; Weltmann, K.-D.; Hackbarth, C.; Heidecke, C.-D.; Von Bernstorff, W.; Von Woedtke, T.; Partecke, L.I. Synergistic inhibition of tumor cell proliferation by cold plasma and gemcitabine. Plasma Process. Polym. 2015, 12, 1377–1382.
  44. Bekeschus, S.; Masur, K.; Kolata, J.; Wende, K.; Schmidt, A.; Bundscherer, L.; Barton, A.; Kramer, A.; Bröker, B.; Weltmann, K.-D. Human Mononuclear Cell Survival and Proliferation is Modulated by Cold Atmospheric Plasma Jet. Plasma Process. Polym. 2013, 10, 706–713.
  45. Bekeschus, S.; Scherwietes, L.; Freund, E.; Liedtke, K.R.; Hackbarth, C.; Von Woedtke, T.; Partecke, L.-I. Plasma-treated medium tunes the inflammatory profile in murine bone marrow-derived macrophages. Clin. Plasma Med. 2018, 11, 1–9.
  46. Yan, D.; Xiao, H.; Zhu, W.; Nourmohammadi, N.; Zhang, L.G.; Bian, K.; Keidar, M. The role of aquaporins in the anti-glioblastoma capacity of the cold plasma-stimulated medium. J. Phys. D Appl. Phys. 2017, 50, 055401.
  47. Tanaka, H.; Mizuno, M.; Ishikawa, K.; Takeda, K.; Hashizume, H.; Nakamura, K.; Utsumi, F.; Kajiyama, H.; Okazaki, Y.; Toyokuni, S.; et al. Glioblastoma cell lines display different sensitivities to plasma-activated medium. IEEE Trans. Radiat. Plasma Med. Sci. 2017, 2, 99–102.
  48. Utsumi, F.; Kajiyama, H.; Nakamura, K.; Tanaka, H.; Hori, M.; Kikkawa, F. Selective cytotoxicity of indirect nonequilibrium atmospheric pressure plasma against ovarian clear-cell carcinoma. SpringerPlus 2014, 3, 398.
  49. Tanaka, H.; Mizuno, M.; Ishikawa, K.; Nakamura, K.; Utsumi, F.; Kajiyama, H.; Kano, H.; Maruyama, S.; Kikkawa, F.; Hori, M. Cell survival and proliferation signaling pathways are downregulated by plasma-activated medium in glioblastoma brain tumor cells. Plasma Med. 2012, 2, 207–220.
  50. Gandhirajan, R.K.; Rödder, K.; Bodnar, Y.; Pasqual-Melo, G.; Emmert, S.; Griguer, C.E.; Weltmann, K.-D.; Bekeschus, S. Cytochrome C oxidase Inhibition and Cold Plasma-derived Oxidants Synergize in Melanoma Cell Death Induction. Sci. Rep. 2018, 8, 12734.
  51. Yan, D.; Talbot, A.; Nourmohammadi, N.; Cheng, X.; Canady, J.; Sherman, J.H.; Keidar, M. Principles of using Cold Atmospheric Plasma Stimulated Media for Cancer Treatment. Sci. Rep. 2015, 5, 18339.
  52. Boehm, D.; Heslin, C.; Cullen, P.J.; Bourke, P. Cytotoxic and mutagenic potential of solutions exposed to cold atmospheric plasma. Sci. Rep. 2016, 6, 21464.
  53. Girard, P.-M.; Arbabian, A.; Fleury, M.; Bauville, G.; Puech, V.; Dutreix, M.; Sousa, J.S. Synergistic Effect of H2O2 and NO2 in Cell Death Induced by Cold Atmospheric He Plasma. Sci. Rep. 2016, 6, 29098.
  54. Takeda, S.; Yamada, S.; Hattori, N.; Nakamura, K.; Tanaka, H.; Kajiyama, H.; Kanda, M.; Kobayashi, D.; Tanaka, C.; Fujii, T.; et al. Intraperitoneal Administration of Plasma-Activated Medium: Proposal of a Novel Treatment Option for Peritoneal Metastasis From Gastric Cancer. Ann. Surg. Oncol. 2017, 24, 1188–1194.
  55. Mohades, S.; Laroussi, M.; Sears, J.; Barekzi, N.; Razavi, H. Evaluation of the effects of a plasma activated medium on cancer cells. Phys. Plasmas 2015, 22, 122001.
  56. Yan, D.; Sherman, J.H.; Cheng, X.; Ratovitski, E.; Canady, J.; Keidar, M. Controlling plasma stimulated media in cancer treatment application. Appl. Phys. Lett. 2014, 105, 224101.
  57. Judée, F.; Fongia, C.; Ducommun, B.; Yousfi, M.; Lobjois, V.; Merbahi, N. Short and long time effects of low temperature plasma activated media on 3D multicellular tumor spheroids. Sci. Rep. 2016, 6, 21421.
  58. Mohades, S.; Barekzi, N.; Razavi, H.; Maruthamuthu, V.; Laroussi, M. Temporal evaluation of the anti-tumor efficiency of plasma-activated media. Plasma Process. Polym. 2016, 13, 1206–1211.
  59. Van Loenhout, J.; Flieswasser, T.; Boullosa, L.F.; De Waele, J.; Van Audenaerde, J.; Marcq, E.; Jacobs, J.; Lin, A.; Lion, E.; Dewitte, H.; et al. Cold atmospheric plasma-treated PBS eliminates immunosuppressive pancreatic stellate cells and induces immunogenic cell death of pancreatic cancer cells. Cancers 2019, 11, 1597.
  60. Heusler, T.; Bruno, G.; Bekeschus, S.; Lackmann, J.-W.; Von Woedtke, T.; Wende, K. Can the effect of cold physical plasma-derived oxidants be transported via thiol group oxidation? Clin. Plasma Med. 2019, 14, 100086.
  61. Van Boxem, W.; Van Der Paal, J.; Gorbanev, Y.; Vanuytsel, S.; Smits, E.; Dewilde, S.; Bogaerts, A. Anti-cancer capacity of plasma-treated PBS: Effect of chemical composition on cancer cell cytotoxicity. Sci. Rep. 2017, 7, 16478.
  62. Liedtke, K.R.; Bekeschus, S.; Kaeding, A.; Hackbarth, C.; Kuehn, J.-P.; Heidecke, C.-D.; Von Bernstorff, W.; Von Woedtke, T.; Partecke, L.I. Non-thermal plasma-treated solution demonstrates antitumor activity against pancreatic cancer cells in vitro and in vivo. Sci. Rep. 2017, 7, 8319.
  63. Liedtke, K.R.; Freund, E.; Hackbarth, C.; Heidecke, C.-D.; Partecke, L.-I.; Bekeschus, S. A myeloid and lymphoid infiltrate in murine pancreatic tumors exposed to plasma-treated medium. Clin. Plasma Med. 2018, 11, 10–17.
  64. Obeid, M.; Tesniere, A.; Ghiringhelli, F.; Fimia, G.M.; Apetoh, L.; Perfettini, J.-L.; Castedo, M.; Mignot, G.; Panaretakis, T.; Casares, N.; et al. Calreticulin exposure dictates the immunogenicity of cancer cell death. Nat. Med. 2007, 13, 54–61.
  65. Bekeschus, S.; Clemen, R.; Nießner, F.; Sagwal, S.K.; Freund, E.; Schmidt, A. Medical gas plasma jet technology targets murine melanoma in an immunogenic fashion. Adv. Sci. 2020, 7, 1903438.
More
© Text is available under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/)
Academic Video Service
Feedback