4.5 Article

The HSP90 inhibitor 17-AAG potentiates the antileishmanial activity of the ether lipid edelfosine

Journal

ACTA TROPICA
Volume 131, Issue -, Pages 32-36

Publisher

ELSEVIER SCIENCE BV
DOI: 10.1016/j.actatropica.2013.11.018

Keywords

HSP90 inhibitor; 17-AAG; Edelfosine; Cell cycle arrest; Apoptosis-like cell death; Leishmania spp.

Funding

  1. Ministerio de Economia y Competitividad of Spain [SAF2011-30518]
  2. Red Tematica de Investigacion Cooperativa en Cancer
  3. Instituto de Salud Carlos III
  4. Fondo Europeo de Desarrollo Regional of the European Union [RD12/0036/0065]
  5. Junta de Castilla y Leon [C5I052A11-2, CSI221A12-2]
  6. Fundacion Ramon Areces
  7. Ministerio de Ciencia e Innovacion of Spain

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HSP90 is an abundant protein in Leishmania parasites that plays a major role in the parasite survival under stress conditions. Here we found that the HSP90 inhibitor 17-AAG (>= 100 nM 17-AAG) induced cell cycle arrest at G(0)/G(1) in Leishmania infantum and Leishmania panamensis promastigotes, and highly potentiated the induction of cell death by an apoptotic-like process mediated by the ether phospholipid edelfosine (5-20 mu M). These data suggest that the combined treatment of 17-AAG and edelfosine might be a novel and effective approach of combination therapy in the treatment of leishmaniasis. (C) 2013 Elsevier B.V. All rights reserved.

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