期刊
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
卷 6, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fcell.2018.00113
关键词
Warburg effect; breast Cancer; MDIVI-1; cell death; bioenergetics; OXPHOS
资金
- Irish Cancer Society Collaborative Cancer Research Centre BREAST-PREDICT Grant [CCRC13GAL]
- Science Foundation Ireland [13/IA/1881]
- Science Foundation Ireland (SFI) [13/IA/1881] Funding Source: Science Foundation Ireland (SFI)
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.
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