Upregulation of Chemoresistance by Mg<sup>2+</sup> 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<sup>2+</sup> deficiency affects chemosensitivity of cancer cells. Here, we investigated the effect of low Mg<sup>2+</sup> concentration (LM) on proliferat...
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doaj-8a547cd278e64ec49c5c85f53e5083d42021-05-31T23:49:08ZengMDPI AGCells2073-44092021-05-01101179117910.3390/cells10051179Upregulation of Chemoresistance by Mg<sup>2+</sup> Deficiency through Elevation of ATP Binding Cassette Subfamily B Member 1 Expression in Human Lung Adenocarcinoma A549 CellsSaki Onuma0Aya Manabe1Yuta Yoshino2Toshiyuki Matsunaga3Tomohiro Asai4Akira Ikari5Laboratory of Biochemistry, Department of Biopharmaceutical Sciences, Gifu Pharmaceutical University, Gifu 501-1196, JapanLaboratory of Biochemistry, Department of Biopharmaceutical Sciences, Gifu Pharmaceutical University, Gifu 501-1196, JapanLaboratory of Biochemistry, Department of Biopharmaceutical Sciences, Gifu Pharmaceutical University, Gifu 501-1196, JapanEducation Center of Green Pharmaceutical Sciences, Gifu Pharmaceutical University, Gifu 502-8585, JapanDepartment of Medical Biochemistry, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka 422-8526, JapanLaboratory of Biochemistry, Department of Biopharmaceutical Sciences, Gifu Pharmaceutical University, Gifu 501-1196, JapanSeveral anticancer drugs including cisplatin (CDDP) induce hypomagnesemia. However, it remains fully uncertain whether Mg<sup>2+</sup> deficiency affects chemosensitivity of cancer cells. Here, we investigated the effect of low Mg<sup>2+</sup> 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<sup>2+</sup> deficiency reduces the chemotherapy sensitivity of A549 cells, although it suppresses cell proliferation.https://www.mdpi.com/2073-4409/10/5/1179lung adenocarcinomachemoresistanceABCB1hypomagnesemia |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Saki Onuma Aya Manabe Yuta Yoshino Toshiyuki Matsunaga Tomohiro Asai Akira Ikari |
spellingShingle |
Saki Onuma Aya Manabe Yuta Yoshino Toshiyuki Matsunaga Tomohiro Asai Akira Ikari Upregulation of Chemoresistance by Mg<sup>2+</sup> Deficiency through Elevation of ATP Binding Cassette Subfamily B Member 1 Expression in Human Lung Adenocarcinoma A549 Cells Cells lung adenocarcinoma chemoresistance ABCB1 hypomagnesemia |
author_facet |
Saki Onuma Aya Manabe Yuta Yoshino Toshiyuki Matsunaga Tomohiro Asai Akira Ikari |
author_sort |
Saki Onuma |
title |
Upregulation of Chemoresistance by Mg<sup>2+</sup> 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<sup>2+</sup> 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<sup>2+</sup> 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<sup>2+</sup> 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<sup>2+</sup> 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<sup>2+</sup> deficiency through elevation of atp binding cassette subfamily b member 1 expression in human lung adenocarcinoma a549 cells |
publisher |
MDPI AG |
series |
Cells |
issn |
2073-4409 |
publishDate |
2021-05-01 |
description |
Several anticancer drugs including cisplatin (CDDP) induce hypomagnesemia. However, it remains fully uncertain whether Mg<sup>2+</sup> deficiency affects chemosensitivity of cancer cells. Here, we investigated the effect of low Mg<sup>2+</sup> 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<sup>2+</sup> deficiency reduces the chemotherapy sensitivity of A549 cells, although it suppresses cell proliferation. |
topic |
lung adenocarcinoma chemoresistance ABCB1 hypomagnesemia |
url |
https://www.mdpi.com/2073-4409/10/5/1179 |
work_keys_str_mv |
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