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Tumor Biology
Published in: Tumor Biology 11/2016

01-11-2016 | Original Article

TRPM7 channel inhibition mediates midazolam-induced proliferation loss in human malignant glioma

Authors: Jingkao Chen, Yunling Dou, Xiaoke Zheng, Tiandong Leng, Xiaofang Lu, Ying Ouyang, Huawei Sun, Fan Xing, Jialuo Mai, Jiayu Gu, Bingzheng Lu, Guangmei Yan, Jun Lin, Wenbo Zhu

Published in: Tumor Biology | Issue 11/2016

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Abstract

The melastatin-like transient receptor potential 7 (TRPM7) has been implicated in proliferation or apoptosis of some cancers, indicating the potential of TRPM7 as an anti-anaplastic target. Here, we identified the characteristic TRPM7 channel currents in human malignant glioma MGR2 cells, which could be blocked by a pharmacologic inhibitor Gd3+. We mined the clinical sample data from Oncomine Database and found that human malignant glioma tissues expressed higher TRPM7 mRNA than normal brain ones. Importantly, we identified a widely used clinical anesthetic midazolam as a TRPM7 inhibitor. Midazolam treatment for seconds suppressed the TRPM7 currents and calcium influx, and treatment for 48 h inhibited the TRPM7 expression. The inhibitory effect on TRPM7 accounts for the proliferation loss and G0/G1 phase cell cycle arrest induced by midazolam. Our data demonstrates that midazolam represses proliferation of human malignant glioma cells through inhibiting TRPM7 currents, which may be further potentiated by suppressing the expression of TRPM7. Our result indicates midazolam as a pharmacologic lead compound with brain-blood barrier permeability for targeting TRPM7 in the glioma.
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Metadata
Title
TRPM7 channel inhibition mediates midazolam-induced proliferation loss in human malignant glioma
Authors
Jingkao Chen
Yunling Dou
Xiaoke Zheng
Tiandong Leng
Xiaofang Lu
Ying Ouyang
Huawei Sun
Fan Xing
Jialuo Mai
Jiayu Gu
Bingzheng Lu
Guangmei Yan
Jun Lin
Wenbo Zhu
Publication date
01-11-2016
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 11/2016
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-016-5317-2

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