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Inhibition of Glucose Transporters and Glutaminase Synergistically Impairs Tumor Cell Growth

Elena S Reckzeh1, George Karageorgis2, Melanie Schwalfenberg2

  • 1Max Planck Institute of Molecular Physiology, Department of Chemical Biology, Otto-Hahn-Strasse 11, 44227 Dortmund, Germany; Technical University Dortmund, Faculty of Chemistry and Chemical Biology, Otto-Hahn-Strasse 6, 44227 Dortmund, Germany.

Cell Chemical Biology
|July 16, 2019
PubMed

Insights

Researchers discovered Glutor, a potent inhibitor targeting glucose transporters (GLUT-1, -2, -3), to suppress cancer cell growth. Combining Glutor with a glutaminase inhibitor synergistically halts cancer proliferation by blocking key nutrient sources.

Area of Science:

  • Oncology
  • Cancer Metabolism
  • Biochemistry

Background:

  • Cancer cells exhibit altered metabolism, relying on aerobic glycolysis and glutamine.
  • This adaptation involves increased glucose transporter expression (GLUT-1, -3).
  • Targeting glucose uptake and glutamine metabolism presents a potential anti-cancer strategy.

Purpose of the Study:

  • To discover and characterize a novel inhibitor of glucose uptake.
  • To evaluate the efficacy of targeting glucose transporters and glutamine metabolism in cancer cells.

Main Methods:

  • Discovery of Glutor, a potent inhibitor of glucose transporters (GLUT-1, -2, -3).
  • Assessment of Glutor's effect on glycolytic flux and cancer cell line growth.
  • Evaluation of synergistic effects of Glutor combined with glutaminase inhibitor CB-839 in colon cancer cells.

Main Results:

  • Glutor potently and selectively suppressed the growth of various cancer cell lines.
  • Glutor attenuated glycolytic flux.
  • Co-treatment with Glutor and CB-839 demonstrated potent and synergistic inhibition of colon cancer cell growth.

Conclusions:

  • Targeting glucose transporters with Glutor is a viable strategy for cancer therapy.
  • Dual inhibition of glucose uptake and glutamine metabolism offers a synergistic approach to suppress cancer cell growth.
  • This dual approach effectively targets cancer's metabolic plasticity and rescue mechanisms.
Keywords:
GLUT-1GLUT-3Warburg effectco-treatmentglutaminasemetabolic plasticitysmall molecule

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