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Updated: Nov 7, 2025

Flow Cytometry-based Drug Screening System for the Identification of Small Molecules That Promote Cellular Differentiation of Glioblastoma Stem Cells
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Flow Cytometry-based Drug Screening System for the Identification of Small Molecules That Promote Cellular Differentiation of Glioblastoma Stem Cells

Published on: January 10, 2018

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Inhibition of mitochondrial translation suppresses glioblastoma stem cell growth

Denise Sighel1, Michela Notarangelo1, Shintaro Aibara2

  • 1Department CIBIO, University of Trento, Trento 38123, Italy.

Cell Reports
|April 28, 2021
PubMed

Insights

Glioblastoma stem cells (GSCs) are resistant to therapy. Researchers found that targeting mitochondrial translation with the antibiotic quinupristin/dalfopristin (Q/D) effectively suppresses GSC growth and may offer a new cancer treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Glioblastoma stem cells (GSCs) are a major cause of glioblastoma (GBM) treatment resistance.
  • GSCs depend on oxidative phosphorylation (OXPHOS) for survival, a process reliant on mitochondrial translation.

Purpose of the Study:

  • To explore the therapeutic potential of targeting mitochondrial translation in GSCs.
  • To identify compounds that inhibit mitochondrial ribosomes and GSC growth.

Main Methods:

  • High-content screening of mitochondrial ribosome inhibitors.
  • In vitro assays to assess GSC clonogenicity, cell cycle, and apoptosis.
  • Cryo-electron microscopy (cryo-EM) to determine drug-target interactions.

Main Results:

  • Quinupristin/dalfopristin (Q/D) effectively suppresses GSC growth and clonogenicity.
  • Q/D treatment leads to cell cycle dysregulation and apoptosis in GSCs.
  • Cryo-EM revealed Q/D binds to the large mitoribosomal subunit, inhibiting mitochondrial protein synthesis and OXPHOS.

Conclusions:

  • Targeting mitochondrial translation is a promising therapeutic strategy for GBM.
  • Quinupristin/dalfopristin (Q/D) demonstrates potential for repurposing as an anti-cancer agent against glioblastoma.
Keywords:
OXPHOScryo-EMdalfopristindrug repurposingglioblastomaglioblastoma stem cellshigh-content screeningmitochondrial translationmitoribosomequinupristin

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