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Sublethal treatment with plasma-activated medium induces senescence-like growth arrest of A549 cells: involvement of intracellular mobile zinc

Plasma-activated medium (PAM) is a solution produced by exposing a liquid medium to non-thermal atmospheric pressure plasma (NTAPP). A number of reactive molecules, such as reactive oxygen species and reactive nitrogen species, are contained in PAM. Therefore, exposure to high doses of PAM results i...

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Autores principales: Hara, Hirokazu, Kobayashi, Mari, Shiiba, Moe, Kamiya, Tetsuro, Adachi, Tetsuo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: the Society for Free Radical Research Japan 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6667388/
https://www.ncbi.nlm.nih.gov/pubmed/31379409
http://dx.doi.org/10.3164/jcbn.19-17
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author Hara, Hirokazu
Kobayashi, Mari
Shiiba, Moe
Kamiya, Tetsuro
Adachi, Tetsuo
author_facet Hara, Hirokazu
Kobayashi, Mari
Shiiba, Moe
Kamiya, Tetsuro
Adachi, Tetsuo
author_sort Hara, Hirokazu
collection PubMed
description Plasma-activated medium (PAM) is a solution produced by exposing a liquid medium to non-thermal atmospheric pressure plasma (NTAPP). A number of reactive molecules, such as reactive oxygen species and reactive nitrogen species, are contained in PAM. Therefore, exposure to high doses of PAM results in cell death. We previously demonstrated that intracellular zinc (Zn(2+)) serves as an important mediator in PAM-induced cell death; however, the effects of sublethal treatment with PAM on cell functions are not fully understood. In the present study, we found that sublethal PAM treatment suppressed cell proliferation and induced senescence-like changes in lung adenocarcinoma A549 cells. Cell cycle analysis revealed that PAM induced cell cycle arrest at the G2/M phase. PAM increased the level of intracellular free Zn(2+) and the Zn(2+) chelator TPEN counteracted PAM-induced growth suppression, suggesting that Zn(2+) functions in PAM-induced growth suppression. In addition, sublethal treatment with PAM induced phosphorylation of ATM kinase, accumulation of p53 protein, and expression of p21 and GADD45A, which are known p53 target genes, in a Zn(2+)-dependent manner. These results suggest that the induction of growth arrest and cellular senescence by sublethal PAM treatment is mediated by Zn(2+)-dependent activation of the ATM/p53 pathway.
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spelling pubmed-66673882019-08-02 Sublethal treatment with plasma-activated medium induces senescence-like growth arrest of A549 cells: involvement of intracellular mobile zinc Hara, Hirokazu Kobayashi, Mari Shiiba, Moe Kamiya, Tetsuro Adachi, Tetsuo J Clin Biochem Nutr Original Article Plasma-activated medium (PAM) is a solution produced by exposing a liquid medium to non-thermal atmospheric pressure plasma (NTAPP). A number of reactive molecules, such as reactive oxygen species and reactive nitrogen species, are contained in PAM. Therefore, exposure to high doses of PAM results in cell death. We previously demonstrated that intracellular zinc (Zn(2+)) serves as an important mediator in PAM-induced cell death; however, the effects of sublethal treatment with PAM on cell functions are not fully understood. In the present study, we found that sublethal PAM treatment suppressed cell proliferation and induced senescence-like changes in lung adenocarcinoma A549 cells. Cell cycle analysis revealed that PAM induced cell cycle arrest at the G2/M phase. PAM increased the level of intracellular free Zn(2+) and the Zn(2+) chelator TPEN counteracted PAM-induced growth suppression, suggesting that Zn(2+) functions in PAM-induced growth suppression. In addition, sublethal treatment with PAM induced phosphorylation of ATM kinase, accumulation of p53 protein, and expression of p21 and GADD45A, which are known p53 target genes, in a Zn(2+)-dependent manner. These results suggest that the induction of growth arrest and cellular senescence by sublethal PAM treatment is mediated by Zn(2+)-dependent activation of the ATM/p53 pathway. the Society for Free Radical Research Japan 2019-07 2019-06-11 /pmc/articles/PMC6667388/ /pubmed/31379409 http://dx.doi.org/10.3164/jcbn.19-17 Text en Copyright © 2019 JCBN http://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Article
Hara, Hirokazu
Kobayashi, Mari
Shiiba, Moe
Kamiya, Tetsuro
Adachi, Tetsuo
Sublethal treatment with plasma-activated medium induces senescence-like growth arrest of A549 cells: involvement of intracellular mobile zinc
title Sublethal treatment with plasma-activated medium induces senescence-like growth arrest of A549 cells: involvement of intracellular mobile zinc
title_full Sublethal treatment with plasma-activated medium induces senescence-like growth arrest of A549 cells: involvement of intracellular mobile zinc
title_fullStr Sublethal treatment with plasma-activated medium induces senescence-like growth arrest of A549 cells: involvement of intracellular mobile zinc
title_full_unstemmed Sublethal treatment with plasma-activated medium induces senescence-like growth arrest of A549 cells: involvement of intracellular mobile zinc
title_short Sublethal treatment with plasma-activated medium induces senescence-like growth arrest of A549 cells: involvement of intracellular mobile zinc
title_sort sublethal treatment with plasma-activated medium induces senescence-like growth arrest of a549 cells: involvement of intracellular mobile zinc
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6667388/
https://www.ncbi.nlm.nih.gov/pubmed/31379409
http://dx.doi.org/10.3164/jcbn.19-17
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