Metformin enhanced by 2-deoxyglucose (2DG) in cell study

[JimmyToowong]

Targeting cancer cell metabolism: The combination of metformin and 2-deoxyglucose induces p53-dependent apoptosis in prostate cancer cells - Abstract Show Comments PDF Print E-mail

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Monday, 22 March 2010

Institut National de la Sante et de la Recherche Medicale (INSERM), U895, Centre Méditerranéen de Médecine Moléculaire (C3M), Team 7, Cellular and Molecular Physiopathology of Obesity and Diabetes; Université de Nice Sophia-Antipolis, Faculté de Médecine, Institut Signalisation et Pathologies; INSERM, U895, C3M, Team 1; INSERM, U576; INSERM, U634; Université de Nice Sophia-Antipolis, Centre Commun de Microscopie Appliquée; and INSERM, U895, C3M, Team 2, Nice, France.

Targeting cancer cell metabolism is a new promising strategy to fight cancer. Metformin, a widely used antidiabetic agent, exerts antitumoral and antiproliferative action. In this study, the addition of metformin to 2-deoxyglucose (2DG) inhibited mitochondrial respiration and glycolysis in prostate cancer cells leading to a severe depletion in ATP. The combination of the two drugs was much more harmful for cancer cells than the treatment with metformin or 2DG alone, leading to 96% inhibition of cell viability in LNCaP prostate cancer cells. In contrast, a moderate effect on cell viability was observed in normal prostate epithelial cells. At the cellular level, the combination of metformin and 2DG induced p53-dependent apoptosis via the energy sensor pathway AMP kinase, and the reexpression of a functional p53 in p53-deficient prostate cancer cells restored caspase-3 activity. In addition to apoptosis, the combination of metformin and 2DG arrested prostate cancer cells in G(2)-M. This G(2)-M arrest was independent of p53 and correlated with a stronger decrease in cell viability than obtained with either drug. Finally, metformin inhibited 2DG-induced autophagy, decreased beclin 1 expression, and triggered a switch from a survival process to cell death. Our study reinforces the growing interest of metabolic perturbators in cancer therapy and highlights the potential use of the combination of metformin and 2DG as an anticancerous treatment.

Written by:

Ben Sahra I, Laurent K, Giuliano S, Larbret F, Ponzio G, Gounon P, Le Marchand-Brustel Y, Giorgetti-Peraldi S, Cormont M, Bertolotto C, Deckert M, Auberger P, Tanti JF, Bost F.

Reference:

Cancer Res. 2010 Mar 15;70(6):2465-75.

doi:10.1158/0008-5472.CAN-09-2782

PubMed Abstract

PMID:20215500 Forum: Every little bit helps Title: Metformin enhanced by 2-deoxyglucose (2DG) in cell study

Such uses are complicated by the fact that 2-deoxyglucose does have some toxicity.

This extract can be found on http://PubMed.com, and is in the public domain.

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