title: The HSP90 inhibitor 17-AAG potentiates the antileishmanial activity of the ether lipid edelfosine.
abstract: 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.
authors.affiliation: Instituto de Biología Molecular y Celular del Cáncer, Centro de Investigación del Cáncer, CSIC-Universidad de Salamanca, Campus Miguel de Unamuno, Salamanca, Spain.
authors.forename: Rubén E
authors.initials: RE
authors.lastname: Varela-M
authors.affiliation: Instituto de Biología Molecular y Celular del Cáncer, Centro de Investigación del Cáncer, CSIC-Universidad de Salamanca, Campus Miguel de Unamuno, Salamanca, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Mollinedo-Gajate
authors.affiliation: Laboratorio de Inmunología Parasitaria y Molecular, IBSAL-CIETUS, Facultad de Farmacia, Universidad de Salamanca, Campus Miguel de Unamuno, Salamanca, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Muro
authors.affiliation: Instituto de Biología Molecular y Celular del Cáncer, Centro de Investigación del Cáncer, CSIC-Universidad de Salamanca, Campus Miguel de Unamuno, Salamanca, Spain. Electronic address: fmollin@usal.es.
authors.forename: Faustino
authors.initials: F
authors.lastname: Mollinedo
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D016227:Benzoquinones / Q000494:pharmacology*; D003470:Culture Media; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D015870:Gene Expression; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D047029:Lactams, Macrocyclic / Q000494:pharmacology*; D007891:Leishmania / Q000187:drug effects* / Q000254:growth & development; D018314:Leishmania infantum / Q000187:drug effects* / Q000254:growth & development; D010742:Phospholipid Ethers / Q000494:pharmacology*; D015800:Protozoan Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D016192:Resting Phase, Cell Cycle / Q000187:drug effects
chemical_list: D016227:Benzoquinones; D003470:Culture Media; D018841:HSP90 Heat-Shock Proteins; D047029:Lactams, Macrocyclic; D010742:Phospholipid Ethers; D015800:Protozoan Proteins; C026659:edelfosine; C112765:tanespimycin
keywords: 17-AAG; Apoptosis-like cell death; Cell cycle arrest; Edelfosine; HSP90 inhibitor; Leishmania spp.