Cytotoxic Activity of Atmospheric Cold Plasma Jet Towards 3D Human Breast Cancer Cell Model

E. A. Patrakova; Патракова Е. А.; M. M. Birykov; Бирюков М. М.; O. S. Troitskaya; Троицкая О. С.; D. D. Novak; Новак Д. Д.; E. V. Milakhina; Милахина Е. В.; P. P. Gugin; Гугин П. П.; D. E. Zakrevskyc; Закревский Д. Э.; I. V. Schweigert; Швейгерт И. В.; O. A. Koval; Коваль О. А.

doi:10.31857/S004137712301008X

Cytotoxic Activity of Atmospheric Cold Plasma Jet Towards 3D Human Breast Cancer Cell Model

Authors: Patrakova E.A.¹^,2, Birykov M.M.¹^,2^,3, Troitskaya O.S.¹^,3, Novak D.D.¹^,2^,3, Milakhina E.V.⁴^,3, Gugin P.P.⁵^,3, Zakrevskyc D.E.⁴^,5^,3, Schweigert I.V.³, Koval O.A.¹^,2^,3
Affiliations:
1. Institute of Chemical Biology and Fundamental Medicine, SB Russian Academy of Sciences
2. Novosibirsk State University
3. Khristianovich Institute of Theoretical and Applied Mechanics, SB Russian Academy of Sciences
4. Novosibirsk State Technical University
5. Rzhanov Institute of Semiconductor Physics, SB Russian Academy of Sciences
Issue: Vol 65, No 1 (2023)
Pages: 39-53
Section: Articles
URL: https://journals.rcsi.science/0041-3771/article/view/140066
DOI: https://doi.org/10.31857/S004137712301008X
EDN: https://elibrary.ru/GLBBFZ
ID: 140066

Cite item

Full Text

Open Access
Restricted Access

Access granted
Restricted Access

Subscription Access

Abstract
About the authors
References
Supplementary files
Statistics

Abstract

The treatment of solid tumors with a cold atmospheric plasma jet (CAP) is an innovative approach, which began to be actively developed only in the last decade. As a consequence, the studies aimed at revealing the conditions of selectivity of such effects on tumor cells, including in 3D tumor models, are important. It is known that the main cytotoxic effects of CAP are caused by reactive oxygen and nitrogen species, which are formed in the plasma flow and the availability of which for the cells in the classical 2D and 3D cultivation models may be different. We used multicellular spheroids of MCF7-EGFR cells with hyperexpression of epidermal growth factor receptor (EGFR), the parental MCF7 breast adenocarcinoma cell line, and MCF10A non-transformed human breast cells. Irradiation of MCF7-EGFR spheroids led to destruction of multicellular 3D structures into individual cells with activation of death processes. It was shown that cells of CAP-irradiated spheroids underwent phagocytosis by activated macrophages. When comparing direct exposure to CAP and cultivation of MCF7-EGFR spheroids in CAP-irradiated medium (CAP-IM), a higher content of reactive oxygen and nitrogen species in spheroid cells was found when cultured in CAP-IM, which further leads to a greater cytotoxic effect than in direct irradiation. The cytotoxicity of CAP-IM has been shown to be valid longer when such medium is stored at 4 than at −20°С. Thus, it was shown that the treatment of spheroids with CAP-IM was more effective in death induction than direct CAP irradiation.

Keywords

3D spheroids, cold plasma jet, antitumor therapy, reactive oxygen species, EGFR, breast adenocarcinoma

References

Нуштаева А.А., Савинкова М.М., Ермаков М.С., Варламов М.Е., Новак Д.Д., Рихтер В.А., Коваль О.А. 2022. Клетки рака молочной железы изменяют чувствительность к гормональным и ростовым стимулам при 3D культивировании. Цитология Т. 64. С. 353. (Nushtaeva A.A., Savinkova M.M., Ermakov M.S., Varlamov M.E., Novak D.D., Richter V. A., Koval O.A. 2022. Breast cancer cells in 3D model alters their sensitivity to hormonal and growth factors. Сell Tiss. Biol. V. 16. P. 555. )https://doi.org/10.1134/S1990519X22060050
Arfin S., Jha N.K., Jha S.K., Kesari K.K., Ruokolainen J., Roychoudhury S., Rathi B., Kumar D. 2021. Oxidative stress in cancer cell metabolism. Antioxidants. V. 10. P. 642. https://doi.org/10.3390/antiox10050642
Attri P., Kumar N., Park J.H., Yadav D.K., Choi S., Uhm H.S., Kim I.T., Choi E.H., Lee W. 2015. Influence of reactive species on the modification of biomolecules generated from the soft plasma. Sci. Rep. V. 5. P. 8221. https://doi.org/10.1038/srep08221
Bagamanshina A.V., Troitskaya O.S., Nushtaeva A.A., Yunusova A.Y., Starykovych M.O., Kuligina E.V., Kit Y.Y., Richter M., Wohlfromm F., Kähne T., Lavrik I.N., Richter V.A., Koval O.A. 2019. Cytotoxic and antitumor activity of lactaptin in combination with autophagy inducers and inhibitors. BioMed. Res. Int. V. 2019. https://doi.org/10.1155/2019/4087160
Basu P., Taghavi K., Hu, S.-Y., Mogri S., Joshi S. 2018. Management of cervical premalignant lesions. Curr. Probl. Cancer. V. 42. P. 129. https://doi.org/10.1016/j.currproblcancer.2018.01.010
Boehm D., Heslin C., Cullen P.J., Bourke P. 2016. Cytotoxic and mutagenic potential of solutions exposed to cold atmospheric plasma. Sci. Rep. V. 6. P. 21464. https://doi.org/10.1038/srep21464
Chauvin J., Judee F., Merbahi N., Vicendo P. 2018. Effects of plasma activated medium on head and neck FaDu cancerous cells: comparison of 3D and 2D response. ACAMC. V. 18. P. 776. https://doi.org/10.2174/1871520617666170801111055
Colombo E., Cattaneo M.G. 2021. Multicellular 3D models to study tumour-stroma interactions. IJMS. V. 22. P. 1633. https://doi.org/10.3390/ijms22041633
Dai X., Bazaka K., Richard D.J., Thompson E.W., Ostrikov K. 2018. The emerging role of gas plasma in oncotherapy. Trends in Biotechnol. V. 36. P. 1183. https://doi.org/10.1016/j.tibtech.2018.06.010
Domonkos M., Tichá P., Trejbal J., Demo P. 2021. Applications of cold atmospheric pressure plasma technology in medicine, Agriculture Food Industry. Applied Sci. V. 11. P. 4809. https://doi.org/10.3390/app11114809
Ferreira L.P., Gaspar V.M., Mano J.F. 2018. Design of spherically structured 3D in vitro tumor models – advances and prospects. Acta Biomat. V. 75. P. 11. https://doi.org/10.1016/j.actbio.2018.05.034
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. J. Phys. D: Appl. Phys. V. 45. P. 263001. https://doi.org/10.1088/0022-3727/45/26/263001
Judée F., Fongia C., Ducommun B., Yousfi M., Lobjois V., Merbahi N. 2016. Short and long time effects of low temperature plasma activated media on 3D multicellular tumor spheroids. Sci. Rep. V. 6. P. 21421. https://doi.org/10.1038/srep21421
Klinkhammer C., Verlackt C., Smiłowicz D., Kogelheide F., Bogaerts A., Metzler-Nolte N., Stapelmann K., Havenith M., Lackmann J.-W. 2017. Elucidation of plasma-induced chemical modifications on glutathione and glutathione disulphide. Sci. Rep. V. 7. P. 13828. https://doi.org/10.1038/s41598-017-13041-8
Laschke M.W., Menger M.D. 2017. Spheroids as vascularization units: from angiogenesis research to tissue engineering applications. Biotechnol. Advances. V. 35. P. 782. https://doi.org/10.1016/j.biotechadv.2017.07.002
Metelmann H.-R., Nedrelow, D.S., Seebauer, C., Schuster, M., von Woedtke, T., Weltmann, K.D., Kindler S., Metelmann P.H., Finkelstein S.E., Von Hoff D.D., Podmelle F. 2015. Head and neck cancer treatment and physical plasma. Clinical Plasma Med. V. 3. P. 17. https://doi.org/10.1016/j.cpme.2015.02.001
Qu Y., Han B., Yu Y., Yao W., Bose S., Karlan B.Y., Giuliano A.E., Cui X. 2015. Evaluation of MCF10A as a reliable model for normal human mammary epithelial cells. PLoS One. V. 10. P. e0131285. https://doi.org/10.1371/journal.pone.0131285
Salinas-Vera Y.M., Valdés J., Hidalgo-Miranda A., Cisneros-Villanueva M., Marchat L.A., Nuñez-Olvera S.I., Ramos-Payán R., Pérez-Plasencia C., Arriaga-Pizano L.A., Prieto-Chávez J.L., López-Camarillo C. 2022. Three-dimensional organotypic cultures reshape the microRNAs transcriptional program in breast cancer cells. Cancers. V. 14. P. 2490. https://doi.org/10.3390/cancers14102490
Schweigert I., Alexandrov A., Zakrevsky D., Milakhina E., Patrakova E., Troitskaya O., Birykov M., Koval O. 2021. Mismatch of frequencies of ac voltage and streamers propagation in cold atmospheric plasma jet for typical regimes of cancer cell treatment. J. Phys.: Conf. Ser. V. 2100. P. 012020. https://doi.org/10.1088/1742-6596/2100/1/012020
Schweigert I., Zakrevsky D., Gugin P., Yelak E., Golubitskaya E., Troitskaya O., Koval O.: 2019. Interaction of cold atmospheric argon and helium plasma jets with bio-target with grounded substrate beneath. Applied Sci. V. 9. P. 4528. https://doi.org/10.3390/app9214528
Semmler M.L., Bekeschus S., Schäfer M., Bernhardt T., Fischer T., Witzke K., Seebauer C., Rebl H., Grambow E., Vollmar B., Nebe J.B., Metelmann H.-R., Woedtke T. von, Emmert S., Boeckmann L. 2020. Molecular mechanisms of the efficacy of cold atmospheric pressure plasma (CAP) in cancer treatment. Cancers. V. 12. P. 269. https://doi.org/10.3390/cancers12020269
Shashurin A., Stepp M.A., Hawley T.S., Pal-Ghosh S., Brieda L., Bronnikov S., Jurjus R.A., Keidar, M. 2010. Influence of Cold plasma atmospheric jet on surface integrin expression of living cells: influence of cold plasma atmospheric jet on surface integrin expression of living cells. Plasma Processes Polym. V. 7. P. 294. https://doi.org/10.1002/ppap.200900086
Sung H., Ferlay J., Siegel R.L., Laversanne M., Soerjomatara, I., Jemal A., Bray F. 2021. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA A Cancer J. Clin. V. 71. P. 209. https://doi.org/10.3322/caac.21660
Tanaka H., Bekeschus S., Yan D., Hori M., Keidar M., Laroussi M. 2021. Plasma-treated solutions (PTS) in cancer therapy. Cancers. V. 13. P. 1737. https://doi.org/10.3390/cancers13071737
Troitskaya O., Golubitskaya E., Biryukov M., Varlamov M., Gugin P., Milakhina E., Richter V., Schweigert I., Zakrevsky D., Koval O. 2020. Non-thermal plasma application in tumor-bearing mice induces increase of serum HMGB1. Int. J. Mol. Sci. V. 21. P. E5128. https://doi.org/10.3390/ijms21145128
Troitskaya O., Novak D., Nushtaeva A., Savinkova M., Varlamov M., Ermakov M., Richter V., Koval O. 2021. EGFR Transgene stimulates spontaneous formation of MCF7 breast cancer cells spheroids with partly loss of HER3 receptor. IJMS. V. 22. P. 12 937. https://doi.org/10.3390/ijms222312937
Vandamme M., Robert E., Lerondel S., Sarron V., Ries D., Dozias S., Sobilo J., Gosset D., Kieda C., Legrain B., Pouvesle J.-M., Pape A.L. 2012. ROS implication in a new antitumor strategy based on non-thermal plasma. Int. J. Cancer. V. 130. P. 2185. https://doi.org/10.1002/ijc.26252
Verjans E.-T., Doijen J., Luyten W., Landuyt B., Schoofs L. 2018. Three-dimensional cell culture models for anticancer drug screening: Worth the effort? J. Cell Physiol. V. 233. P. 2993. https://doi.org/10.1002/jcp.26052
Wanigasekara J., Barcia C., Cullen P.J., Tiwari B., Curtin J.F. 2022. Plasma induced reactive oxygen species-dependent cytotoxicity in glioblastoma 3D tumourspheres. Plasma Processes Polymers. V. 19. P. 2100157. https://doi.org/10.1002/ppap.202100157
Wiegand C., Fink S., Beier O., Horn K., Pfuch A., Schimanski A., Grünler B., Hipler U.-C., Elsner P. 2016. Dose- and time-dependent cellular effects of cold atmospheric pressure plasma evaluated in 3D skin models. Skin Pharmacol. Physiol. V. 29. P. 257. https://doi.org/10.1159/000450889
Xu D., Wang B., Xu Y., Chen Z., Cui Q., Yang Y., Chen H., Kong M.G. 2016. Intracellular ROS mediates gas plasma-facilitated cellular transfection in 2D and 3D cultures. Sci. Rep. V. 6. P. 27872. https://doi.org/10.1038/srep27872
Yazdani M. 2015. Concerns in the application of fluorescent probes DCDHF-DA, DHR 123 and DHE to measure reactive oxygen species in vitro. Toxicol. in Vitro. V. 30. P. 578. https://doi.org/10.1016/j.tiv.2015.08.010
Yousfi M., Merbahi N., Pathak A., Eichwald O. 2014. Low-temperature plasmas at atmospheric pressure: toward new pharmaceutical treatments in medicine. Fundam. Clin. Pharmacol. V. 28. P. 123. https://doi.org/10.1111/fcp.12018