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Cytotoxic Activity of a Cold Atmospheric Plasma Jet in Relation to a 3D Cell Model of Human Breast Cancer

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Abstract

The treatment of solid tumors by a cold atmospheric plasma (CAP) jet is an innovative approach that has been actively developed only in the last decade. As a result, studies aimed at identifying the conditions for selective effect on tumor cells, including as parts of 3D models that mimic malignant neoplasms are pertinent. It is known that the main cytotoxic effects of a CAP are caused by reactive oxygen and nitrogen species in the plasma jet. Their availability for cells in classical 2D and 3D models of cell cultivation may be different. Here, we used multicellular spheroids of MCF7–EGFR cells with overexpression of the epidermal growth-factor receptor (EGFR), cells of parental breast adenocarcinoma MCF7 cell line, and nontransformed human breast cells MCF10A. Irradiation of MCF7–EGFR spheroids induced destruction of multicellular 3D structures into individual cells and activated cell death. It has been shown that the cells of irradiated spheroids undergo phagocytosis by activated macrophages. Comparison of a direct CAP irradiation of MCF7–EGFR spheroids and indirect treatment with plasma-activated medium (PAM) revealed a higher content of reactive oxygen and nitrogen species in spheroid cells cultivated in the irradiated medium. It produced a higher cytotoxic effect than direct irradiation. It has been shown that the cytotoxic properties of PAM are better preserved when such a medium is stored at 4° than at –20°C. Thus, the death of tumor cells in spheroids was more effective with addition of the culture medium irradiated with a CAP than direct irradiation of cells.

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Funding

This work was supported by the Russian Foundation for Basic Research (project no. 20-34-90021), and studies on optimizing the specific effect of a CAP in adhesive cell cultures were supported of the Russian Science Foundation (project no. 19-19-00255-P).

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Authors and Affiliations

  1. Institute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of Sciences, 630090, Novosibirsk, Russia

    E. A. Patrakova, M. M. Biryukov, O. S. Troitskaya, D. D. Novak & O. A. Koval

  2. Novosibirsk State University, 630090, Novosibirsk, Russia

    E. A. Patrakova, M. M. Biryukov, D. D. Novak & O. A. Koval

  3. Khristianovich Institute of Theoretical and Applied Mechanics, Siberian Branch, Russian Academy of Sciences, 630090, Novosibirsk, Russia

    M. M. Biryukov, O. S. Troitskaya, D. D. Novak, E. V. Milakhina, D. E. Zakrevsky, I. V. Schweigert & O. A. Koval

  4. Novosibirsk State Technical University, 630073, Novosibirsk, Russia

    E. V. Milakhina & D. E. Zakrevsky

  5. Rzhanov Institute of Semiconductor Physics, Siberian Branch, Russian Academy of Sciences, 630090, Novosibirsk, Russia

    P. P. Gugin & D. E. Zakrevsky

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  1. E. A. Patrakova
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  2. M. M. Biryukov
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  3. O. S. Troitskaya
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  6. P. P. Gugin
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  7. D. E. Zakrevsky
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  8. I. V. Schweigert
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  9. O. A. Koval
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E.A. Patrakova and M.M. Biryukov made an equal contribution.

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Correspondence to M. M. Biryukov.

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The authors declare that they have no conflicts of interest. Experiments involving animals or human beings have not been performed.

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Abbreviations: RNS—reactive nitrogen species; ROS—reactive oxygen species; GMS—grounded metal substrate; MTT reagent—3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide; BC—breast cancer; PAM—plasma-activated medium; UVR—ultraviolet radiation; CAP—cold atmospheric plasma; EGFR—epidermal growth-factor receptor; H2DCFDA—2',7'-dichlorodihydrofluorescein diacetate; PMA—phorbol-12-myristate 13-acetate.

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Patrakova, E.A., Biryukov, M.M., Troitskaya, O.S. et al. Cytotoxic Activity of a Cold Atmospheric Plasma Jet in Relation to a 3D Cell Model of Human Breast Cancer. Cell Tiss. Biol. 17, 233–246 (2023). https://doi.org/10.1134/S1990519X23030094

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