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 (≥100 nM 17-AAG) induced cell cycle arrest at G0/G1 in L. infantum and L. panamensis promastigotes, and highly potentiated the induction of cell death by an apoptotic-like process mediated by the ether phospholipid edelfosine (5-20 μM). 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.

• Autores: Varela Miranda, Rubén Eduardo; Mollinedo Gajate, Cristina; Muro, Antonio; Mollinedo, Faustino
• Tipo de recurso: Article of investigation
• Fecha de publicación: 2014
• Institución: Universidad de Antioquia
• Repositorio: Repositorio UdeA
• Idioma: eng
• OAI Identifier: oai:bibliotecadigital.udea.edu.co:10495/33047
• Acceso en línea: https://hdl.handle.net/10495/33047
• Palabra clave: Proteínas HSP90 de Choque Térmico; HSP90 Heat-Shock Proteins; Puntos de Control del Ciclo Celular; Cell Cycle Checkpoints; Leishmania; Leishmania infantum; Apoptosis; Benzoquinonas; Benzoquinones; Relación Dosis-Respuesta a Droga; Dose-Response Relationship, Drug; Quimioterapia Combinada; Drug Therapy, Combination; Éteres Fosfolípidos; Phospholipid Ethers; Proteínas Protozoarias; Protozoan Proteins; Fase de Descanso del Ciclo Celular; Resting Phase, Cell Cycle
• Rights: openAccess
• License: http://creativecommons.org/licenses/by-nc-nd/2.5/co/