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

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 (≥100nM 17-AAG) induced cell cycle arrest at G0/G1 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 (5-20μM). 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.This work was supported by grants from Ministerio de Economía y Competitividad of Spain (SAF2011-30518), Red Temática de Investigación Cooperativa en Cáncer, Instituto de Salud Carlos III, cofunded by the Fondo Europeo de Desarrollo Regional of the European Union (RD12/0036/0065), Junta de Castilla y León (CSI052A11-2 and CSI221A12-2), and Fundación Ramón Areces 2010-13. REVM was supported by a Torres Quevedo fellowship from the Ministerio de Ciencia e Innovación of Spain.European Community’s Seventh Framework Programme FP7-2007-2013 (grant HEALTH-F2-2011-256986 - PANACREAS).Peer Reviewe