GPR17 signaling activation by CHBC agonist induced cell death via modulation of MAPK pathway in glioblastoma

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Translational Orthotopic Models of Glioblastoma Multiforme
07:37

Translational Orthotopic Models of Glioblastoma Multiforme

Published on: February 17, 2023

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Phung Nguyen1, Phuong Doan1, Akshaya Murugesan2

  • 1Molecular Signaling Lab, Faculty of Medicine and Health Technology, Tampere University, Tampere 33720, Finland; BioMeditech and Tays Cancer Center, Tampere University Hospital, P.O. Box 553, 33101 Tampere, Finland.

Life Sciences
|January 12, 2022
PubMed
Abstract

Insights

A novel compound, CHBC, effectively inhibits glioblastoma multiforme (GBM) cell growth by inducing apoptosis and cell cycle arrest. This indole derivative targets G-protein-coupled receptor 17, offering a potential new therapeutic strategy for aggressive brain tumors.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Glioblastoma multiforme (GBM) is an aggressive primary adult brain tumor known for its cellular heterogeneity and resistance to chemotherapy.
  • Novel therapeutic agents targeting specific GBM biomarkers are needed to overcome treatment resistance.

Purpose of the Study:

  • To investigate the molecular mechanisms underlying the anti-cancer effects of a novel indole derivative, CHBC, in GBM cells.
  • To characterize the efficiency of CHBC as an agonist targeting G-protein-coupled receptor 17 (GPR17) and its role in GBM cell death induction.

Main Methods:

  • Time-dependent inhibitor assays were performed on LN229 and SNB19 glioblastoma cell lines to assess CHBC's inhibitory effects.
  • Cell cycle arrest was measured using propidium iodide (PI) staining and image analysis.
  • Apoptosis induction, caspase 3/7 activity, mitochondrial membrane potential, and MAPK signaling pathway modulation were analyzed using specific assays and immunoblotting.

Main Results:

  • CHBC demonstrated time-dependent inhibition of SNB19 and LN229 cell growth, with an IC50 of 85 μM.
  • CHBC induced cell death via apoptosis, characterized by caspase 3/7 activation and mitochondrial membrane potential dysfunction, and caused G2/M cell cycle arrest.
  • MAPK signaling pathway disruption was confirmed, supporting CHBC's anticancer effects.

Conclusions:

  • CHBC effectively induces G2/M cell cycle arrest and apoptosis in human glioblastoma cells by disrupting the MAPK signaling pathway.
  • These findings suggest that CHBC represents a promising new class of compounds for the treatment of glioblastoma.
Keywords:
ApoptosisGlioblastoma multiformeIndole derivativeMAPK pathwayMechanism of action

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