Oncotarget

Research Papers:

Inhibition of TRPM7 by carvacrol suppresses glioblastoma cell proliferation, migration and invasion

Wen-Liang Chen, Andrew Barszczyk, Ekaterina Turlova, Marielle Deurloo, Baosong Liu, Burton B. Yang, James T. Rutka, Zhong-Ping Feng and Hong-Shuo Sun _

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Oncotarget. 2015; 6:16321-16340. https://doi.org/10.18632/oncotarget.3872

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Abstract

Wen-Liang Chen1,2, Andrew Barszczyk2, Ekaterina Turlova1,2, Marielle Deurloo2, Baosong Liu1,2, Burton B. Yang4, James T. Rutka1, Zhong-Ping Feng2 and Hong-Shuo Sun1,2,3,5

1 Department of Surgery, University of Toronto, Toronto, Canada

2 Department of Physiology, University of Toronto, Toronto, Canada

3 Department of Pharmacology, University of Toronto, Toronto, Canada

4 Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada

5 Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, Canada

Correspondence to:

Hong-Shuo Sun, email:

Zhong-Ping Feng, email:

Keywords: glioblastoma, carvacrol, TRPM7, cell viability, migration, invasion

Received: November 24, 2014 Accepted: April 02, 2015 Published: April 19, 2015

Abstract

Glioblastomas are progressive brain tumors with devastating proliferative and invasive characteristics. Ion channels are the second largest target class for drug development. In this study, we investigated the effects of the TRPM7 inhibitor carvacrol on the viability, resistance to apoptosis, migration, and invasiveness of the human U87 glioblastoma cell line.

The expression levels of TRPM7 mRNA and protein in U87 cells were detected by RT-PCR, western blotting and immunofluorescence. TRPM7 currents were recorded using whole-cell patch-clamp techniques. An MTT assay was used to assess cell viability and proliferation. Wound healing and transwell experiments were used to evaluate cell migration and invasion. Protein levels of p-Akt/t-Akt, p-ERK1/2/t-ERK1/2, cleaved caspase-3, MMP-2 and phosphorylated cofilin were also detected.

TRPM7 mRNA and protein expression in U87 cells is higher than in normal human astrocytes. Whole-cell patch-clamp recording showed that carvacrol blocks recombinant TRPM7 current in HEK293 cells and endogenous TRPM7-like current in U87 cells. Carvacrol treatment reduced the viability, migration and invasion of U87 cells. Carvacrol also decreased MMP-2 protein expression and promoted the phosphorylation of cofilin. Furthermore, carvacrol inhibited the Ras/MEK/MAPK and PI3K/Akt signaling pathways.

Therefore, carvacrol may have therapeutic potential for the treatment of glioblastomas through its inhibition of TRPM7 channels.


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