TY - JOUR

T1 - Cytotoxic Activity of a Cold Atmospheric Plasma Jet in Relation to a 3D Cell Model of Human Breast Cancer

AU - Patrakova, E. A.

AU - Biryukov, M. M.

AU - Troitskaya, O. S.

AU - Novak, D. D.

AU - Milakhina, E. V.

AU - Gugin, P. P.

AU - Zakrevsky, D. E.

AU - Schweigert, I. V.

AU - Koval, O. A.

N1 - 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). Публикация для корректировки.

PY - 2023/6

Y1 - 2023/6

N2 - 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.

AB - 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.

KW - 3D spheroids

KW - anticancer therapy

KW - breast adenocarcinoma

KW - cold plasma jet

KW - epidermal growth-factor receptor

KW - reactive oxygen species

UR - https://www.scopus.com/record/display.uri?eid=2-s2.0-85161044818&origin=inward&txGid=e58fc3f7ea4d3f9620355e300d263ed7

UR - https://www.mendeley.com/catalogue/02e34834-212c-3358-9415-c79dc32ec72b/

U2 - 10.1134/S1990519X23030094

DO - 10.1134/S1990519X23030094

M3 - Article

VL - 17

SP - 233

EP - 246

JO - Cell and Tissue Biology

JF - Cell and Tissue Biology

SN - 1990-519X

IS - 3

ER -