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Metabolic Targeting of Breast Cancer Cells With the 2-Deoxy-D-Glucose and the Mitochondrial Bioenergetics Inhibitor MDIVI-1.

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posted on 22.11.2019 by Federico Lucantoni, Heiko Düssmann, Jochen HM Prehn

Breast cancer cells have different requirements on metabolic pathways in order to sustain their growth. Triple negative breast cancer (TNBC), an aggressive breast cancer subtype relies mainly on glycolysis, while estrogen receptor positive (ER+) breast cancer cells possess higher mitochondrial oxidative phosphorylation (OXPHOS) levels. However, breast cancer cells generally employ both pathways to sustain their metabolic needs and to compete with the surrounding environment. In this study, we demonstrate that the mitochondrial fission inhibitor MDIVI-1 alters mitochondrial bioenergetics, at concentrations that do not affect mitochondrial morphology. We show that this effect is accompanied by an increase in glycolysis consumption. Dual targeting of glycolysis with 2-deoxy-D-glucose (2DG) and mitochondrial bioenergetics with MDIVI-1 reduced cellular bioenergetics, increased cell death and decreased clonogenic activity of MCF7 and HDQ-P1 breast cancer cells. In conclusion, we have explored a novel and effective combinatorial regimen for the treatment of breast cancer.

Funding

Irish Cancer Society Collaborative Cancer Research Centre BREAST-PREDICT. Science Foundation Ireland.

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The original article is available at www.frontiersin.org

Published Citation

Lucantoni F, Dussmann H, Prehn JHM. Metabolic Targeting of Breast Cancer Cells With the 2-Deoxy-D-Glucose and the Mitochondrial Bioenergetics Inhibitor MDIVI-1. Frontiers in Cell and Developmental Biology. 2018;6:113

Publication Date

11/09/2018

Publisher

Frontiers

PubMed ID

30255019

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