Reference : Peripheral benzodiazepine receptor (PBR) ligand cytotoxicity unrelated to PBR expression
Scientific journals : Article
Human health sciences : Pharmacy, pharmacology & toxicology
http://hdl.handle.net/2268/4842
Peripheral benzodiazepine receptor (PBR) ligand cytotoxicity unrelated to PBR expression
English
Hans, Grégory mailto [Centre Hospitalier Universitaire de Liège - CHU > > Anesthésie et réanimation >]
Wislet, Sabine mailto [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Biochimie et physiologie générales, et biochimie humaine >]
Lallemend, François [Université de Liège - ULg > Centre of Cellular and Molecular Neurobiology]
Robe, Pierre mailto [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Génétique générale et humaine >]
Rogister, Bernard mailto [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Biochimie et physiologie générales, et biochimie humaine >]
Belachew, Shibeshih mailto [Université de Liège - ULg > Département des sciences cliniques > Neurologie >]
Nguyen, Laurent mailto [Université de Liège - ULg > Département des sciences cliniques > Neurologie >]
Malgrange, Brigitte mailto [Université de Liège - ULg > > CNCM/ Centre fac. de rech. en neurobiologie cell. et moléc. >]
Moonen, Gustave mailto [Université de Liège - ULg > Département des sciences cliniques > Neurologie - Doyen de la Faculté de Médecine]
Rigo, Jean-Michel [Universiteit Hasselt - UH > > > >]
1-Mar-2005
Biochemical Pharmacology
Pergamon-Elsevier Science Ltd
69
5
819-830
Yes (verified by ORBi)
International
0006-2952
Oxford
[en] peripheral benzodiazepine receptor ; apoptosis ; cancer ; ligands ; mitochondria ; necrosis
[en] Some synthetic ligands of the peripheral-type benzodiazepine receptor (PBR), an 18 kDa protein of the outer mitochondrial membrane, are cytotoxic for several tumor cell lines and arise as promising chemotherapeutic candidates. However, conflicting results were reported regarding the actual effect of these drugs on cellular survival ranging from protection to toxicity. Moreover, the concentrations needed to observe such a toxicity were usually high, far above the affinity range for their receptor, hence questioning its specificity. In the present study, we have shown that micromolar concentrations of FGIN-1-27 And Ro 5-4864, two chemically unrelated PBR ligands are toxic for both PBR-expressing SK-N-BE neuroblastoma cells and PBR-deficient Jurkat lymphoma cells. We have thereby demonstrated that the cytotoxicity of these drugs is unrelated to their PBR-binding activity. Moreover, Ro 54864-induced cell death differed strikingly between both cell types, being apoptotic in Jurkat cells while necrotic in SK-N-BE cells. Again, this did not seem to be related to PBR expression since Ro 5-4864-induced death of PBR-transfected Jurkat cells remained apoptotic. Taken together, our results show that PBR is unlikely to mediate all the effects of these PBR ligands. They however confirm that some of these ligands are very effective cytotoxic drugs towards various cancer cells, even for reputed chemoresistant tumors such as neuroblastoma, and, surprisingly, also for PBR-lacking tumor cells. (C) 2004 Elsevier Inc. All rights reserved.
Researchers ; Professionals
http://hdl.handle.net/2268/4842
10.1016/j.bcp.2004.11.029

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