Delta-2-troglitazone sensitizez triple-negative breast cancer cells to chemotherapy: a consequence of mitochondrial dysfunction? - Archive ouverte HAL Accéder directement au contenu
Poster De Conférence Année : 2015

Delta-2-troglitazone sensitizez triple-negative breast cancer cells to chemotherapy: a consequence of mitochondrial dysfunction?

Résumé

Background: Thiazolidinediones display antiproliferative effects which could result of mechanisms altering cell metabolism. Our objectives are to characterize the modifications of the triple-negative breast cancer cell line MDA-MB231 metabolism after Delta-2-Troglitazone (D2T) exposure and to define whether D2T could potentiate the action of chemotherapeutic agents. Methods: NAD+ and NADH concentrations were determined by chemiluminescence. Lactate and glucose concentrations were measured with an YSI 2950 Biochemistry Analyzer. Mitochondrial activity was assessed by oxygraphy. Results: NAD+/NADH ratio was increased after a 24h treatment, suggesting that glycolysis and/or mitochondrial respiration could be altered. Oxygen consumption was diminished after a 24h exposure to D2T or one of its derivatives, associated with a decreased mitochondrial efficiency and a mitochondrial decoupling. At the glycolytic level, lactate production and glucose consumption were increased. Finally, low doses of D2T potentiated the effects of 2-Deoxyglucose and doxorubicin on cell viability. Conclusion: D2T derivatives target mitochondria likely leading to the stimulation of glycolysis. A low dose of D2T potentiates the action of 2-Deoxyglucose and doxorubicin on cell viability. The impact of the D2T/doxorubicin combination on proliferation and apoptosis has to be characterized. Overall, the link between the mitochondrial dysfunction observed with D2T and its antiproliferative effect has to be demonstrated.

Domaines

Cancer
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Dates et versions

hal-01214922 , version 1 (13-10-2015)

Identifiants

  • HAL Id : hal-01214922 , version 1

Citer

Audrey Berthe, Stéphanie Grandemange, Michel Boisbrun, Bost Frédéric, Marie Zaffino, et al.. Delta-2-troglitazone sensitizez triple-negative breast cancer cells to chemotherapy: a consequence of mitochondrial dysfunction?. 6th World Congress on Targeting Mitochondria, Oct 2015, Berlin, Germany. 2015. ⟨hal-01214922⟩
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