TRPM7 channel inhibition mediates midazolam-induced proliferation loss in human malignant glioma
| Autor: | Jiayu Gu, Huawei Sun, Bingzheng Lu, Jialuo Mai, Xiaofang Lu, Jun Lin, Guangmei Yan, Ying Ouyang, Yunling Dou, Wenbo Zhu, Fan Xing, Tiandong Leng, Xiaoke Zheng, Jingkao Chen |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Cell cycle checkpoint Databases Factual Midazolam Blotting Western Fluorescent Antibody Technique TRPM Cation Channels chemistry.chemical_element Apoptosis Protein Serine-Threonine Kinases Pharmacology Calcium Biology Real-Time Polymerase Chain Reaction 03 medical and health sciences Transient receptor potential channel 0302 clinical medicine TRPM7 Glioma Image Processing Computer-Assisted Tumor Cells Cultured medicine Data Mining Humans RNA Messenger RNA Small Interfering Cell Proliferation Messenger RNA Reverse Transcriptase Polymerase Chain Reaction Cell Cycle General Medicine medicine.disease 030104 developmental biology Anti-Anxiety Agents chemistry 030220 oncology & carcinogenesis medicine.drug |
| Zdroj: | Tumor Biology. 37:14721-14731 |
| ISSN: | 1423-0380 1010-4283 |
| DOI: | 10.1007/s13277-016-5317-2 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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