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Extracellular Glucose Depletion as an Indirect Measure of Glucose Uptake in Cells and Tissues Ex Vivo
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Identification of Compounds That Decrease Glioblastoma Growth and Glucose Uptake in Vitro

Catherine J Landis1, Sixue Zhang2, Gloria A Benavides3

  • 1Department of Cell, Developmental and Integrative Biology , University of Alabama at Birmingham , Birmingham , Alabama , United States.

ACS Chemical Biology
|June 16, 2018
PubMed

Insights

Novel GLUT inhibitors were identified to target glioblastoma (GBM) tumor-initiating cells. These compounds reduce glucose uptake and GBM cell growth, offering a potential new therapeutic strategy for aggressive brain cancers.

Area of Science:

  • Oncology
  • Cancer Metabolism
  • Neuro-oncology

Background:

  • Tumor heterogeneity in glioblastoma (GBM) hinders effective therapies.
  • Brain tumor-initiating cells (BTICs) drive GBM growth and exhibit metabolic plasticity.
  • GLUT3 is upregulated in BTICs, supporting survival in nutrient-poor environments.

Purpose of the Study:

  • To identify novel inhibitors targeting glucose transporter 3 (GLUT3) in GBM.
  • To evaluate the efficacy of identified inhibitors against GBM cells and BTICs.
  • To explore targeting metabolic reprogramming as a therapeutic strategy for GBM.

Main Methods:

  • Structure-based virtual screening (SBVS) was employed to identify potential GLUT inhibitors.
  • In vitro assays assessed the impact of compounds on GBM cell growth and glucose uptake.
  • Glycolytic stress tests were performed on patient-derived xenograft (PDX) cells.

Main Results:

  • Two novel compounds, SRI-37683 and SRI-37684, were identified through SBVS.
  • These compounds selectively inhibited GBM cell growth with minimal toxicity to normal cells.
  • Inhibition of glucose uptake, glycolytic capacity, and reserve capacity was observed in GBM PDX cells.

Conclusions:

  • Targeting GLUT3 offers a promising therapeutic avenue for glioblastoma.
  • Novel GLUT inhibitors demonstrate potential for treating GBM and other cancers.
  • SRI-37683 and SRI-37684 serve as valuable lead compounds for further drug development.

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