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Advanced Neurology

ORIGINAL RESEARCH ARTICLE
In vitro suppression of glioblastoma cell

functions by TG100-115, a transient receptor
potential melastatin 7 kinase inhibitor

Yuanyuan Xu 1,2† , Wenliang Chen 1,2† , Rahmah Alanazi , Xinyang Zhang 1,2 ,
1,2
Erin Cross 2 , Barbara Gundi 1,2 , James T. Rutka 1 , F. David Horgen 3 ,
Andrea Fleig 4,5 , Zhong-Ping Feng 2 , and Hong-Shuo Sun 1,2,6,7*
1 Department of Surgery, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
2 Department of Physiology, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
3 Department of Natural Science, College of Natural Sciences and Computational Sciences, Hawaii
Pacific University, Honolulu, Hawaii, United States of America
4 John A. Burns School of Medicine and University of Hawaii Cancer Center at the University of
Hawaii at Manoa, Honolulu, Hawaii, United States of America
5 Center for Biomedical Research at The Queen’s Medical Center, Honolulu, Hawaii, United States
of America
6 Department of Pharmacology, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario,
Canada
7 Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada
(This article belongs to the Special Issue: Advanced Neurology 3 Anniversary Special Issue)
rd

† These authors contributed equally
to this work. Abstract
*Corresponding author:
Hong-Shuo Sun Glioblastomas (GBMs) are highly aggressive and lethal primary brain tumors, known for
(hss.sun@utoronto.ca) their rapid proliferation, diffuse infiltration, and resistance to conventional therapies.
Recent studies have highlighted the involvement of transient receptor potential
Citation: Xu Y, Chen W,
Alanazi R, et al. In vitro suppression melastatin 7 (TRPM7) in regulating GBM progression through its dual function as an
of glioblastoma cell functions by ion channel and a serine/threonine protein kinase. TG100-115, initially characterized
TG100-115, a transient receptor as a phosphoinositide 3-kinase γ/δ inhibitor, has recently been identified as a novel
potential melastatin 7 kinase
inhibitor. Adv Neurol. 2025; inhibitor of TRPM7 kinase. However, its potential pharmacological effects in GBM cells
4(3):88-99. have not been fully elucidated. In this study, we investigated the anti-GBM effects of
doi: 10.36922/AN025110023 TG100-115 in U251 glioma cells. Cell viability and proliferation were assessed using
Received: March 14, 2025 the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, whereas cell
Revised: May 26, 2025 motility and invasiveness were determined through wound healing and transwell assays,
respectively. Western blotting was used to detect the expression of key proteins involved
Accepted: May 30, 2025 in the apoptotic and molecular signaling pathways. Our findings revealed that TG100-
Published online: July 11, 2025 115 significantly diminished the viability of U251 cells by promoting apoptosis while
Copyright: © 2025 Author(s). concurrently inhibiting the migratory and invasive activities of GBM cells. Mechanistically,
This is an Open-Access article TG100-115 enhanced apoptotic signaling by modulating B-cell lymphoma 2 (Bcl-2), Bcl-
distributed under the terms of the 2-associated X protein, and cleaved caspase-3 levels. It also altered the phosphorylation
Creative Commons Attribution
License, permitting distribution, status of protein kinase B and cofilin – both critical for cell survival and cytoskeletal
and reproduction in any medium, dynamics. In conclusion, these findings suggest that TG100-115, by targeting TRPM7
provided the original work is kinase, exhibits promising therapeutic potential for GBM treatment and provides novel
properly cited.
insights into targeting TRPM7-associated pathways in aggressive brain tumors.
Publisher’s Note: AccScience
Publishing remains neutral with Keywords: Transient receptor potential melastatin 7 kinase; TG100-115; Glioblastoma;
regard to jurisdictional claims in
published maps and institutional Proliferation; Migration; Invasion
affiliations.
Volume 4 Issue 3 (2025) 88 doi: 10.36922/AN025110023