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

Federico Lucantoni, Heiko Dussmann, Jochen H. M. 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.