Abstract
Plasma technology has recently been one of the potential candidates for the targeted treatment of cancers. In this work, Nightingale®, a non-thermal air plasma jet device, was used to activate lactated Ringer’s injection (LRI) for the in vitro inactivation of lung cancer cells—A549 and H1299. The optimal treatment condition and its effects on the cell cytotoxicity of lung cancer cells were evaluated. Optical emission spectroscopy (OES) and gas detection results indicated gas phase reactive oxygen and nitrogen species (RONS) can be controlled and precisely calculated from plasma dissipated power. For plasma-activated LRI (PA-LRI), concentrations of H2O2, NO3−, and NO2−, as well as their shelf lives, were investigated. Two-hour treatment of PA-LRI on A549 and H1299 cells resulted in 92% and 70% cell death, respectively. While the non-cancerous cell, human lung fibroblast (HLF), was not affected neither in terms of cell death or morphological change. To elucidate the mechanisms of the tumor cell cytotoxicity induced by PA-LRI, common active species generated in PA-LRI (H2O2, NO2−, NO3−) were tested. Results showed that H2O2 alone can induce 72% of cell death, compared to PA-LRI, while it was 19% and 2% for NO2− and NO3− respectively. The addition of catalase, which degrades H2O2, reduced cell death induced by PA-LRI and H2O2 to 9% and 6%, respectively. These suggest H2O2 is the main player in PA-LRI-induced lung cancer cell death in vitro. Our discoveries not only benefit the effective usage of plasma-activated LRI but also the applications of plasma technology in medical fields.
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References
Thana P, Wijaikhum A, Poramapijitwat P et al (2019) A compact pulse-modulation cold air plasma jet for the inactivation of chronic wound bacteria: development and characterization. Heliyon 5:e02455. https://doi.org/10.1016/j.heliyon.2019.e02455
Thana P, Kuensaen C, Poramapijitwat P et al (2020) A compact pulse-modulation air plasma jet for the inactivation of chronic wound bacteria: bactericidal effects & host safety. Surf Coat Technol. https://doi.org/10.1016/j.surfcoat.2020.126229
Kosumsupamala K, Thana P, Palee N et al (2022) Air to H2–N2 pulse plasma jet for in-vitro plant tissue culture process: source characteristics. Plasma Chem Plasma Process 42:535–559. https://doi.org/10.1007/s11090-022-10228-4
Verlackt CCW, Van Boxem W, Bogaerts A (2018) Transport and accumulation of plasma generated species in aqueous solution. Phys Chem Chem Phys 20:6845–6859. https://doi.org/10.1039/c7cp07593f
Girard F, Peret M, Dumont N et al (2018) Correlations between gaseous and liquid phase chemistries induced by cold atmospheric plasmas in a physiological buffer. Phys Chem Chem Phys 20:9198–9210. https://doi.org/10.1039/C8CP00264A
Baskar R, Lee KA, Yeo R et al (2012) Cancer and radiation therapy: current advances and future directions. Int J Med Sci 9:193–199. https://doi.org/10.7150/ijms.3635
Newhauser WD, Berrington De Gonzalez A, Schulte R et al (2016) A review of radiotherapy-induced late effects research after advanced technology treatments. Front Oncol 6:13. https://doi.org/10.3389/fonc.2016.00013
Nurgali K, Jagoe RT, Abalo R (2018) Editorial: adverse effects of cancer chemotherapy: anything new to improve tolerance and reduce sequelae? Front Pharmacol 9:245. https://doi.org/10.3389/fphar.2018.00245
Pearce A, Haas M, Viney R et al (2017) Incidence and severity of self-reported chemotherapy side effects in routine care: a prospective cohort study. PLoS ONE 12:e0184360. https://doi.org/10.1371/journal.pone.0184360
Tanaka H, Mizuno M, Ishikawa K et al (2018) New hopes for plasma-based cancer treatment. Plasma 1:150–155. https://doi.org/10.3390/plasma1010014
Von Woedtke T, Reuter S, Masur K et al (2013) Plasmas for medicine. Phys Rep 530:291–320. https://doi.org/10.1016/j.physrep.2013.05.005
Karki SB, Gupta TT, Yildirim-Ayan E et al (2017) Investigation of non-thermal plasma effects on lung cancer cells within 3D collagen matrices. J Phys D Appl Phys 50:315401. https://doi.org/10.1088/1361-6463/aa7b10
Tanaka H, Nakamura K, Mizuno M et al (2016) Non-thermal atmospheric pressure plasma activates lactate in Ringer’s solution for anti-tumor effects. Sci Rep 6:36282. https://doi.org/10.1038/srep36282
Saadati F, Mahdikia H, Abbaszadeh HA et al (2018) Comparison of direct and indirect cold atmospheric-pressure plasma methods in the B16F10 melanoma cancer cells treatment. Sci Rep 8:7689. https://doi.org/10.1038/s41598-018-25990-9
Nupangtha W, Kuensaen C, Ngamjarurojana A et al (2021) A surface dielectric barrier discharge non-thermal plasma to induce cell death in colorectal cancer cells. AIP Adv 11:075222. https://doi.org/10.1063/5.0053501
Raud S, Raud J, Jõgi I et al (2021) The production of plasma activated water in controlled ambient gases and its impact on cancer cell viability. Plasma Chem Plasma Process 41:1381–1395. https://doi.org/10.1007/s11090-021-10183-6
Muneekaew S, Huang YH, Wang M-J (2021) Selective killing effects of atmospheric pressure plasma jet on human melanoma and lewis lung carcinoma cells. Plasma Chem Plasma Process 41:1613–1629. https://doi.org/10.1007/s11090-021-10197-0
Chen Z, Cheng X, Lin L et al (2017) Cold atmospheric plasma discharged in water and its potential use in cancer therapy. J Phys D Appl Phys 50:015208. https://doi.org/10.1088/1361-6463/50/1/015208
Gay-Mimbrera J, Garcia MC, Isla-Tejera B et al (2016) Clinical and biological principles of cold atmospheric plasma application in skin cancer. Adv Ther 33:894–909. https://doi.org/10.1007/s12325-016-0338-1
Metelmann H-R, Seebauer C, Miller V et al (2018) Clinical experience with cold plasma in the treatment of locally advanced head and neck cancer. Clin Plasma Med 9:6–13. https://doi.org/10.1016/j.cpme.2017.09.001
Azzariti A, Iacobazzi RM, Di Fonte R et al (2019) Plasma-activated medium triggers cell death and the presentation of immune activating danger signals in melanoma and pancreatic cancer cells. Sci Rep 9:4099. https://doi.org/10.1038/s41598-019-40637-z
Matsuzaki T, Kano A, Kamiya T et al (2018) Enhanced ability of plasma-activated lactated Ringer’s solution to induce A549cell injury. Arch Biochem Biophys 656:19–30. https://doi.org/10.1016/j.abb.2018.08.011
Bekeschus S, Freund E, Spadola C et al (2019) Risk assessment of kINPen plasma treatment of four human pancreatic cancer cell lines with respect to metastasis. Cancers (Basel) 11(9):1237. https://doi.org/10.3390/cancers11091237
Song C-H, Attri P, Ku S-K et al (2021) Cocktail of reactive species generated by cold atmospheric plasma: oral administration induces non-small cell lung cancer cell death. J Phys D Appl Phys 54:185202. https://doi.org/10.1088/1361-6463/abdff2
Yoshikawa N, Liu W, Nakamura K et al (2020) Plasma-activated medium promotes autophagic cell death along with alteration of the mTOR pathway. Sci Rep 10:1614. https://doi.org/10.1038/s41598-020-58667-3
Van Boxem W, Van Der Paal J, Gorbanev Y et al (2017) Anti-cancer capacity of plasma-treated PBS: effect of chemical composition on cancer cell cytotoxicity. Sci Rep 7:16478. https://doi.org/10.1038/s41598-017-16758-8
Kang SK, Kim HY, Yun GS et al (2015) Portable microwave air plasma device for wound healing. Plasma Sour Sci Technol 24(3):035020. https://doi.org/10.1088/0963-0252/24/3/035020
Duan J, Lu X, He G (2017) The selective effect of plasma activated medium in an in vitro co-culture of liver cancer and normal cells. J Appl Phys 121(1):013302. https://doi.org/10.1063/1.4973484
Kaushik N, Uddin N, Sim GB et al (2015) Responses of solid tumor cells in DMEM to reactive oxygen species generated by non-thermal plasma and chemically induced ROS systems. Sci Rep 5:8587. https://doi.org/10.1038/srep08587
Kaushik NK, Ghimire B, Li Y et al (2018) Biological and medical applications of plasma-activated media, water and solutions. Biol Chem 400:39–62. https://doi.org/10.1515/hsz-2018-0226
Machala Z, Tarabová B, Sersenová D et al (2019) Chemical and antibacterial effects of plasma activated water: correlation with gaseous and aqueous reactive oxygen and nitrogen species, plasma sources and air flow conditions. J Phys D Appl Phys 52(3):034002. https://doi.org/10.1088/1361-6463/aae807
Risa Vaka M, Sone I, Garcia Alvarez R et al (2019) Towards the next-generation disinfectant: composition, storability and preservation potential of plasma activated water on baby spinach leaves. Foods 8(12):692. https://doi.org/10.3390/foods8120692
Sklias K, Santos Sousa J, Girard P-M (2021) Role of short- and long-lived reactive species on the selectivity and anti-cancer action of plasma treatment in vitro. Cancers 13:615. https://doi.org/10.3390/cancers13040615
Bisag A, Bucci C, Coluccelli S et al (2020) Plasma-activated Ringer’s lactate solution displays a selective cytotoxic effect on ovarian cancer cells. Cancers (Basel) 12(2):476. https://doi.org/10.3390/cancers12020476
Reuter S, Von Woedtke T, Weltmann K-D (2018) The kINPen—a review on physics and chemistry of the atmospheric pressure plasma jet and its applications. J Phys D Appl Phys 51(23):233001. https://doi.org/10.1088/1361-6463/aab3ad
Bruggeman PJ, Kushner MJ, Locke BR et al (2016) Plasma–liquid interactions: a review and roadmap. Plasma Sour Sci Technol. https://doi.org/10.1088/0963-0252/25/5/053002
Małajowicz J, Khachatryan K, Kozłowska M (2022) Properties of water activated with low-temperature plasma in the context of microbial activity. Beverages 8(4):63. https://doi.org/10.3390/beverages8040063
Thirumdas R, Kothakota A, Annapure U et al (2018) Plasma activated water (PAW): chemistry, physico-chemical properties, applications in food and agriculture. Trends Food Sci Technol 77:21–31. https://doi.org/10.1016/j.tifs.2018.05.007
Lukes P, Dolezalova E, Sisrova I et al (2014) Aqueous-phase chemistry and bactericidal effects from an air discharge plasma in contact with water: evidence for the formation of peroxynitrite through a pseudo-second-order post-discharge reaction of H2O2and HNO2. Plasma Sour Sci Technol 23:015019. https://doi.org/10.1088/0963-0252/23/1/015019
Heirman P, Van Boxem W, Bogaerts A (2019) Reactivity and stability of plasma-generated oxygen and nitrogen species in buffered water solution: a computational study. Phys Chem Chem Phys 21:12881–12894. https://doi.org/10.1039/c9cp00647h
Kim H-S, Wright KC, Hwang I-W et al (2013) Concentration of hydrogen peroxide generated by gliding arc discharge and inactivation of E. coli in water. Int Commun Heat Mass Transf 42:5–10. https://doi.org/10.1016/j.icheatmasstransfer.2012.12.004
Yong HI, Park J, Kim H-J et al (2018) An innovative curing process with plasma-treated water for production of loin ham and for its quality and safety. Plasma Process Polym 15:1700050. https://doi.org/10.1002/ppap.201700050
Jung S, Kim HJ, Park S et al (2015) The use of atmospheric pressure plasma-treated water as a source of nitrite for emulsion-type sausage. Meat Sci 108:132–137. https://doi.org/10.1016/j.meatsci.2015.06.009
Chauvin J, Judée F, Yousfi M et al (2017) Analysis of reactive oxygen and nitrogen species generated in three liquid media by low temperature helium plasma jet. Sci Rep 7:4562. https://doi.org/10.1038/s41598-017-04650-4
Machala Z, Tarabova B, Hensel K et al (2013) Formation of ROS and RNS in water electro-sprayed through transient spark discharge in air and their bactericidal effects. Plasma Process Polym 10:649–659. https://doi.org/10.1002/ppap.201200113
Mošovská S, Medvecká V, Klas M et al (2022) Decontamination of Escherichia coli on the surface of soybean seeds using plasma activated water. Lwt 154:112720. https://doi.org/10.1016/j.lwt.2021.112720
Miebach L, Freund E, Cecchini AL et al (2022) Conductive gas plasma treatment augments tumor toxicity of Ringer’s lactate solutions in a model of peritoneal carcinomatosis. Antioxidants (Basel) 11(8):1439. https://doi.org/10.3390/antiox11081439
Adachi T, Tanaka H, Nonomura S et al (2015) Plasma-activated medium induces A549 cell injury via a spiral apoptotic cascade involving the mitochondrial-nuclear network. Free Radic Biol Med 79:28–44. https://doi.org/10.1016/j.freeradbiomed.2014.11.014
Adachi T, Matsuda Y, Ishii R et al (2020) Ability of plasma-activated acetated Ringer’s solution to induce A549 cell injury is enhanced by a pre-treatment with histone deacetylase inhibitors. J Clin Biochem Nutr 67:232–239. https://doi.org/10.3164/jcbn.19-104
Hara H, Sueyoshi S, Taniguchi M et al (2017) Differences in intracellular mobile zinc levels affect susceptibility to plasma-activated medium-induced cytotoxicity. Free Radic Res 51:306–315. https://doi.org/10.1080/10715762.2017.1309527
Kumar N, Park JH, Jeon SN et al (2016) The action of microsecond-pulsed plasma-activated media on the inactivation of human lung cancer cells. J Phys D Appl Phys 49(11):115401. https://doi.org/10.1088/0022-3727/49/11/115401
Yan D, Talbot A, Nourmohammadi N et al (2015) Toward understanding the selective anticancer capacity of cold atmospheric plasma–a model based on aquaporins (Review). Biointerphases 10:040801. https://doi.org/10.1116/1.4938020
Yoon YK, Kim HP, Han SW et al (2010) KRAS mutant lung cancer cells are differentially responsive to MEK inhibitor due to AKT or STAT3 activation: implication for combinatorial approach. Mol Carcinog 49:353–362. https://doi.org/10.1002/mc.20607
Vaughan CA, Singh S, Windle B et al (2012) p53 mutants induce transcription of NF-κB2 in H1299 cells through CBP and STAT binding on the NF-κB2 promoter and gain of function activity. Arch Biochem Biophys 518:79–88. https://doi.org/10.1016/j.abb.2011.12.006
Tanaka H, Maeda S, Nakamura K et al (2021) Plasma-activated Ringer’s lactate solution inhibits the cellular respiratory system in HeLa cells. Plasma Process Polym 18(10):2100056. https://doi.org/10.1002/ppap.202100056
Tanaka H, Hosoi Y, Ishikawa K et al (2021) Low temperature plasma irradiation products of sodium lactate solution that induce cell death on U251SP glioblastoma cells were identified. Sci Rep 11:18488. https://doi.org/10.1038/s41598-021-98020-w
Sato Y, Yamada S, Takeda S et al (2018) Effect of plasma-activated lactated Ringer’s solution on pancreatic cancer cells in vitro and in vivo. Ann Surg Oncol 25:299–307. https://doi.org/10.1245/s10434-017-6239-y
Xu S, Wang Y, Que Y et al (2020) Cold atmospheric plasmaactivated Ringer’s solution inhibits the proliferation of osteosarcoma cells through the mitochondrial apoptosis pathway. Oncol Rep 43:1683–1691. https://doi.org/10.3892/or.2020.7518
Adachi T, Nonomura S, Horiba M et al (2016) Iron stimulates plasma-activated medium-induced A549 cell injury. Sci Rep 6:20928. https://doi.org/10.1038/srep20928
Ahn HJ, Kim KI, Kim G et al (2011) Atmospheric-pressure plasma jet induces apoptosis involving mitochondria via generation of free radicals. PLoS ONE 6:e28154. https://doi.org/10.1371/journal.pone.0028154
Acknowledgements
This research work was partially supported by Chiang Mai University, the Plasma and Beam Physics (PBP) Research Center, Department of Physics and Material Sciences, and Department of Biology, Faculty of Science, Chiang Mai University. Especially, we would like to thank Tarinee Boonyawan for English editing.
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Poramapijitwat, P., Thana, P., Sukum, P. et al. Selective Cytotoxicity of Lung Cancer Cells—A549 and H1299—Induced by Ringer's Lactate Solution Activated by a Non-thermal Air Plasma Jet Device, Nightingale®. Plasma Chem Plasma Process 43, 805–830 (2023). https://doi.org/10.1007/s11090-023-10330-1
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DOI: https://doi.org/10.1007/s11090-023-10330-1