Co-treatment of breast cancer cells with pharmacologic doses of 2-deoxy-D-glucose and metformin: Starving tumors

  • Authors:
    • Ulrike Wokoun
    • Martin Hellriegel
    • Günter Emons
    • Carsten Gründker
  • View Affiliations

  • Published online on: March 6, 2017     https://doi.org/10.3892/or.2017.5491
  • Pages: 2418-2424
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Abstract

A characteristic of tumor cells is the increased aerobic glycolysis for energy production. Thus, inhibition of glycolysis represents a selective therapeutic option. It has been shown that glycolysis inhibitor 2-deoxy-D-glucose (2DG) induces apoptotic cell death in different tumor entities. In addition, the antitumor activity of the anti-diabetic drug metformin has been demonstrated. In the present study, we aimed to ascertain whether the combination of pharmacologic doses of 2DG with metformin increases the antitumor efficacy. Cell viability of MDA-MB-231 and HCC1806 triple-negative breast cancer (TNBC) cells treated without or with 2DG or with metformin alone or with the combination of both agents was measured using Alamar Blue assay. Induction of apoptosis was quantified by measurement of the loss of mitochondrial membrane potential and cleavage of PARP. Treatment of breast cancer cells with glycolysis inhibitor 2DG or with the anti-diabetic drug metformin resulted in a significant decrease in cell viability and an increase in apoptosis. Treatment with 2DG in combination with metformin resulted in significantly reduced viability compared with the single agent treatments. The observed reduction in viability was due to induction of apoptosis. In addition, in regards to apoptosis induction a stronger effect in the case of co-treatment compared with single agent treatments was observed. The glycolytic phenotype of human breast cancer cells can be targeted for therapeutic intervention. Co-treatment with doses of the glycolysis inhibitor 2DG and anti-diabetic drug metformin is tolerable in humans and may be a suitable therapy for human breast cancers.
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April-2017
Volume 37 Issue 4

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Wokoun U, Hellriegel M, Emons G and Gründker C: Co-treatment of breast cancer cells with pharmacologic doses of 2-deoxy-D-glucose and metformin: Starving tumors. Oncol Rep 37: 2418-2424, 2017
APA
Wokoun, U., Hellriegel, M., Emons, G., & Gründker, C. (2017). Co-treatment of breast cancer cells with pharmacologic doses of 2-deoxy-D-glucose and metformin: Starving tumors. Oncology Reports, 37, 2418-2424. https://doi.org/10.3892/or.2017.5491
MLA
Wokoun, U., Hellriegel, M., Emons, G., Gründker, C."Co-treatment of breast cancer cells with pharmacologic doses of 2-deoxy-D-glucose and metformin: Starving tumors". Oncology Reports 37.4 (2017): 2418-2424.
Chicago
Wokoun, U., Hellriegel, M., Emons, G., Gründker, C."Co-treatment of breast cancer cells with pharmacologic doses of 2-deoxy-D-glucose and metformin: Starving tumors". Oncology Reports 37, no. 4 (2017): 2418-2424. https://doi.org/10.3892/or.2017.5491