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Upregulation of Chemoresistance by Mg(2+) Deficiency through Elevation of ATP Binding Cassette Subfamily B Member 1 Expression in Human Lung Adenocarcinoma A549 Cells

Several anticancer drugs including cisplatin (CDDP) induce hypomagnesemia. However, it remains fully uncertain whether Mg(2+) deficiency affects chemosensitivity of cancer cells. Here, we investigated the effect of low Mg(2+) concentration (LM) on proliferation and chemosensitivity using human lung...

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Autores principales: Onuma, Saki, Manabe, Aya, Yoshino, Yuta, Matsunaga, Toshiyuki, Asai, Tomohiro, Ikari, Akira
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8150369/
https://www.ncbi.nlm.nih.gov/pubmed/34066059
http://dx.doi.org/10.3390/cells10051179
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author Onuma, Saki
Manabe, Aya
Yoshino, Yuta
Matsunaga, Toshiyuki
Asai, Tomohiro
Ikari, Akira
author_facet Onuma, Saki
Manabe, Aya
Yoshino, Yuta
Matsunaga, Toshiyuki
Asai, Tomohiro
Ikari, Akira
author_sort Onuma, Saki
collection PubMed
description Several anticancer drugs including cisplatin (CDDP) induce hypomagnesemia. However, it remains fully uncertain whether Mg(2+) deficiency affects chemosensitivity of cancer cells. Here, we investigated the effect of low Mg(2+) concentration (LM) on proliferation and chemosensitivity using human lung adenocarcinoma A549 cells. Cell proliferation was reduced by continuous culture with LM accompanied with the elevation of G1 phase proportion. The amounts of reactive oxygen species (ROS) and stress makers such as phosphorylated-ataxia telangiectasia mutated and phosphorylated-p53 were increased by LM. Cell injury was dose-dependently increased by anticancer drugs such as CDDP and doxorubicin (DXR), which were suppressed by LM. Similar results were obtained by roscovitine, a cell cycle inhibitor. These results suggest that LM induces chemoresistance mediated by ROS production and G1 arrest. The mRNA and protein levels of ATP binding cassette subfamily B member 1 (ABCB1) were increased by LM and roscovitine. The LM-induced elevation of ABCB1 and nuclear p38 expression was suppressed by SB203580, a p38 MAPK inhibitor. PSC833, an ABCB1 inhibitor, and SB203580 rescued the sensitivity to anticancer drugs. In addition, cancer stemness properties were suppressed by SB203580. We suggest that Mg(2+) deficiency reduces the chemotherapy sensitivity of A549 cells, although it suppresses cell proliferation.
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spelling pubmed-81503692021-05-27 Upregulation of Chemoresistance by Mg(2+) Deficiency through Elevation of ATP Binding Cassette Subfamily B Member 1 Expression in Human Lung Adenocarcinoma A549 Cells Onuma, Saki Manabe, Aya Yoshino, Yuta Matsunaga, Toshiyuki Asai, Tomohiro Ikari, Akira Cells Article Several anticancer drugs including cisplatin (CDDP) induce hypomagnesemia. However, it remains fully uncertain whether Mg(2+) deficiency affects chemosensitivity of cancer cells. Here, we investigated the effect of low Mg(2+) concentration (LM) on proliferation and chemosensitivity using human lung adenocarcinoma A549 cells. Cell proliferation was reduced by continuous culture with LM accompanied with the elevation of G1 phase proportion. The amounts of reactive oxygen species (ROS) and stress makers such as phosphorylated-ataxia telangiectasia mutated and phosphorylated-p53 were increased by LM. Cell injury was dose-dependently increased by anticancer drugs such as CDDP and doxorubicin (DXR), which were suppressed by LM. Similar results were obtained by roscovitine, a cell cycle inhibitor. These results suggest that LM induces chemoresistance mediated by ROS production and G1 arrest. The mRNA and protein levels of ATP binding cassette subfamily B member 1 (ABCB1) were increased by LM and roscovitine. The LM-induced elevation of ABCB1 and nuclear p38 expression was suppressed by SB203580, a p38 MAPK inhibitor. PSC833, an ABCB1 inhibitor, and SB203580 rescued the sensitivity to anticancer drugs. In addition, cancer stemness properties were suppressed by SB203580. We suggest that Mg(2+) deficiency reduces the chemotherapy sensitivity of A549 cells, although it suppresses cell proliferation. MDPI 2021-05-12 /pmc/articles/PMC8150369/ /pubmed/34066059 http://dx.doi.org/10.3390/cells10051179 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Onuma, Saki
Manabe, Aya
Yoshino, Yuta
Matsunaga, Toshiyuki
Asai, Tomohiro
Ikari, Akira
Upregulation of Chemoresistance by Mg(2+) Deficiency through Elevation of ATP Binding Cassette Subfamily B Member 1 Expression in Human Lung Adenocarcinoma A549 Cells
title Upregulation of Chemoresistance by Mg(2+) Deficiency through Elevation of ATP Binding Cassette Subfamily B Member 1 Expression in Human Lung Adenocarcinoma A549 Cells
title_full Upregulation of Chemoresistance by Mg(2+) Deficiency through Elevation of ATP Binding Cassette Subfamily B Member 1 Expression in Human Lung Adenocarcinoma A549 Cells
title_fullStr Upregulation of Chemoresistance by Mg(2+) Deficiency through Elevation of ATP Binding Cassette Subfamily B Member 1 Expression in Human Lung Adenocarcinoma A549 Cells
title_full_unstemmed Upregulation of Chemoresistance by Mg(2+) Deficiency through Elevation of ATP Binding Cassette Subfamily B Member 1 Expression in Human Lung Adenocarcinoma A549 Cells
title_short Upregulation of Chemoresistance by Mg(2+) Deficiency through Elevation of ATP Binding Cassette Subfamily B Member 1 Expression in Human Lung Adenocarcinoma A549 Cells
title_sort upregulation of chemoresistance by mg(2+) deficiency through elevation of atp binding cassette subfamily b member 1 expression in human lung adenocarcinoma a549 cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8150369/
https://www.ncbi.nlm.nih.gov/pubmed/34066059
http://dx.doi.org/10.3390/cells10051179
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