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Ali 2019 MiP2019

From Bioblast
Sameh Ali
Differential role of mitochondria in rescuing glycolytically inhibited subpopulation of triple negative breast cancer cells.

Link: MiP2019

Ali SS (2019)

Event: MiP2019


Cancer transformations profoundly alters cellular metabolism by increasing glucose consumption via glycolysis to support tumorigenesis. 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. Here we confirm that relative to ER-positive cells (MCF7), TNBC cells (MBA-MD-231) rely more on glycolysis thus providing 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 ฮผM while 40 ฮผM 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 ฮผM. This resilient TNBC cell population showed lower apoptotic markers, moderately lowered ROS, and significantly greater count of cells with active mitochondria. To understand the mechanism of survival we studied metabolic modulations associated with acute and extended treatment with IA. 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.

โ€ข Bioblast editor: Plangger M, Tindle-Solomon L โ€ข O2k-Network Lab: EG Cairo Ali SS

Labels: MiParea: Pharmacology;toxicology  Pathology: Cancer 

Regulation: Inhibitor 


Tumor Biology Research Program, Children's Cancer Hospital Egypt, Cairo, Egypt