Reda 2019 Sci Rep

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Reda A, Refaat A, Abd-Rabou AA, Mahmoud AM, Adel M, Sabet S, Ali SS (2019) Role of mitochondria in rescuing glycolytically inhibited subpopulation of triple negative but not hormone-responsive breast cancer cells. Sci Rep 9:13748.

» PMID: 31551501 Open Access

Reda A, Refaat A, Abd-Rabou AA, Mahmoud AM, Adel M, Sabet S, Ali SS (2019) Sci Rep

Abstract: Triple-negative breast cancer (TNBC) subtype is among the most aggressive cancers with the worst prognosis and least therapeutic targetability while being more likely to spread and recur. Cancer transformations profoundly alter cellular metabolism by increasing glucose consumption via glycolysis to support tumorigenesis. Here we confirm that relative to ER-positive cells (MCF7), TNBC cells (MBA-MD-231) rely more on glycolysis thus providing a rationale to target these cells with glycolytic inhibitors. Indeed, iodoacetate (IA), an effective GAPDH inhibitor, caused about 70% drop in MDA-MB-231 cell viability at 20 μM while 40 μM IA was needed to decrease MCF7 cell viability only by 30% within 4 hours of treatment. However, the triple negative cells showed strong ability to recover after 24 h whereas MCF7 cells were completely eliminated at concentrations <10 μM. To understand the mechanism of MDA-MB-231 cell survival, we studied metabolic modulations associated with acute and extended treatment with IA. The resilient TNBC cell population showed a significantly greater count of cells with active mitochondria, lower apoptotic markers, normal cell cycle regulations, moderately lowered ROS, but increased mRNA levels of p27 and PARP1; all compatible with enhanced cell survival. Our results highlight an interplay between PARP and mitochondrial oxidative phosphorylation in TNBC that comes into play in response to glycolytic disruption. In the light of these findings, we suggest that combined treatment with PARP and mitochondrial inhibitors may provide novel therapeutic strategy against TNBC.


Bioblast editor: Plangger M O2k-Network Lab: EG Cairo Ali SS


Labels: MiParea: Respiration, Pharmacology;toxicology  Pathology: Cancer 

Organism: Human  Tissue;cell: Endothelial;epithelial;mesothelial cell  Preparation: Permeabilized cells 


Coupling state: LEAK, OXPHOS  Pathway: N, S, CIV, ROX  HRR: Oxygraph-2k 

2019-09, Labels