∆2-Troglitazone and 2-Deoxyglucose inhibit breast cancer cell proliferation: a consequence of the alteration of the cancer cell metabolism? - Archive ouverte HAL Accéder directement au contenu
Communication Dans Un Congrès Année : 2014

∆2-Troglitazone and 2-Deoxyglucose inhibit breast cancer cell proliferation: a consequence of the alteration of the cancer cell metabolism?

Résumé

Background: Resistance to conventional therapies and the absence of targeted therapy for triple negative mammary tumors are strong arguments for the search for new therapeutic agents. In cancer cells, the dependency on glycolysis for energy generation provides a biochemical basis to preferentially kill the malignant cells by inhibiting glycolysis. Thiazolidinediones display antiproliferative effects in vitro and in vivo which could be the result of mechanisms targeting cell metabolism. Our objective is to characterize the modifications of breast cancer cell metabolism after ∆2-Troglitazone (∆2T) exposure and to compare it with the effects of 2-deoxyglucose (2-DG), a well known inhibitor of glucose metabolism.Methods: The triple-negative breast cancer cell line MDA-MB231 cells were exposed to D2T and 2-DG. Cell numbers were assessed by crystal violet staining assay. Cell proliferation was determined by BrDU incorporation assay. Gene expression was analysed by RT-PCR. Protein expression was analyzed by immunoblotting and immunolocalisation.Results: 48h cell treatment with increasing concentrations of D2T (0-100µM) and 2-DG (0-10mM) inhibited cell proliferation in a dose-dependent manner. Nevertheless, cell viability was not as much affected suggesting that D2T and 2-DG mainly slowed down cell cycle. Concomitantly, both compounds induced endoplasmic reticulum stress. In contrast to 2-DG, the effect of D2T was not reversed by addition of an excess of glucose. At the metabolic level, NAD+/NADH ratio was increased after a 24h treatment with D2T or 2-DG. Under the same conditions, the mRNA levels of two key glycolysis enzymes, hexokinase and phosphofructokinase, were reduced.Conclusion: Our studies show that ∆2T and 2-DG induce changes in triple-negative breast cancer cell metabolism. The importance of the metabolic deregulation in the antitumoral effect of ∆2T has now to be demonstrated.

Domaines

Cancer
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Dates et versions

hal-01094607 , version 1 (12-12-2014)

Identifiants

  • HAL Id : hal-01094607 , version 1

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Audrey Berthe, Michel Boisbrun, Stéphane Flament, Sabine Mazerbourg. ∆2-Troglitazone and 2-Deoxyglucose inhibit breast cancer cell proliferation: a consequence of the alteration of the cancer cell metabolism?. 8ème forum du Cancéropôle Grand-Est, Nov 2014, Strasbourg, France. ⟨hal-01094607⟩
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