RRC ID 69770
Author Onuma S, Manabe A, Yoshino Y, Matsunaga T, Asai T, Ikari A.
Title Upregulation of Chemoresistance by Mg2+ Deficiency through Elevation of ATP Binding Cassette Subfamily B Member 1 Expression in Human Lung Adenocarcinoma A549 Cells.
Journal Cells
Abstract Several anticancer drugs including cisplatin (CDDP) induce hypomagnesemia. However, it remains fully uncertain whether Mg2+ deficiency affects chemosensitivity of cancer cells. Here, we investigated the effect of low Mg2+ 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 Mg2+ deficiency reduces the chemotherapy sensitivity of A549 cells, although it suppresses cell proliferation.
Volume 10(5)
Published 2021-5-12
DOI 10.3390/cells10051179
PII cells10051179
PMID 34066059
PMC PMC8150369
MeSH A549 Cells ATP Binding Cassette Transporter, Subfamily B / metabolism Adenocarcinoma of Lung / drug therapy* Adenocarcinoma of Lung / metabolism* Cell Cycle Cell Proliferation Cisplatin / administration & dosage Cyclosporins / pharmacology DNA Damage Doxorubicin / administration & dosage Drug Resistance, Neoplasm* Gene Expression Regulation, Neoplastic / drug effects Humans Imidazoles / pharmacology Lung Neoplasms / drug therapy* Lung Neoplasms / metabolism* Lymph Nodes / pathology Magnesium / chemistry* Phosphorylation Pyridines / pharmacology Reactive Oxygen Species Roscovitine / pharmacology p38 Mitogen-Activated Protein Kinases / metabolism
IF 4.366
Human and Animal Cells A549(RCB0098)