title: Perifosine Mechanisms of Action in Leishmania Species.
abstract: Here the mechanism by which perifosine induced cell death inLeishmania donovaniandLeishmania amazonensisis described. The drug reducedLeishmaniamitochondrial membrane potential and decreased cellular ATP levels while increasing phosphatidylserine externalization. Perifosine did not increase membrane permeabilization. We also found that the drug inhibited the phosphorylation of Akt in the parasites. These results highlight the potential use of perifosine as an alternative to miltefosine againstLeishmania.
authors.affiliation: Centre for Integrative Physiology, Biomedical Sciences, Edinburgh Medical School, University of Edinburgh, Edinburgh, United Kingdom atlopez@ull.edu.es.|University Institute of Tropical Diseases and Public Health of the Canary Islands, University of La Laguna, Canary Islands, Spain.
authors.forename: Atteneri
authors.initials: A
authors.lastname: López-Arencibia
authors.affiliation: University Institute of Tropical Diseases and Public Health of the Canary Islands, University of La Laguna, Canary Islands, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Martín-Navarro
authors.affiliation: Laboratoire Matériaux-Molécules et Applications, University of Carthage, La Marsa, Tunisia.
authors.forename: Ines
authors.initials: I
authors.lastname: Sifaoui
authors.affiliation: University Institute of Tropical Diseases and Public Health of the Canary Islands, University of La Laguna, Canary Islands, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Reyes-Batlle
authors.affiliation: University Institute of Tropical Diseases and Public Health of the Canary Islands, University of La Laguna, Canary Islands, Spain.|Cátedra de Parasitología, Escuela de Bioanálisis, Universidad Central de Venezuela, Venezuela.
authors.forename: Carolina
authors.initials: C
authors.lastname: Wagner
authors.affiliation: University Institute of Tropical Diseases and Public Health of the Canary Islands, University of La Laguna, Canary Islands, Spain.
authors.forename: Jacob
authors.initials: J
authors.lastname: Lorenzo-Morales
authors.affiliation: Centre for Integrative Physiology, Biomedical Sciences, Edinburgh Medical School, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Sutherland K
authors.initials: SK
authors.lastname: Maciver
authors.affiliation: University Institute of Tropical Diseases and Public Health of the Canary Islands, University of La Laguna, Canary Islands, Spain.
authors.forename: José E
authors.initials: JE
authors.lastname: Piñero
mesh_terms: D000255:Adenosine Triphosphate / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D000981:Antiprotozoal Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015870:Gene Expression; D020128:Inhibitory Concentration 50; D007893:Leishmania donovani / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D007894:Leishmania mexicana / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D010718:Phosphatidylserines / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D010767:Phosphorylcholine / Q000031:analogs & derivatives* / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D015800:Protozoan Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
chemical_list: D000981:Antiprotozoal Agents; D010718:Phosphatidylserines; D015800:Protozoan Proteins; D010767:Phosphorylcholine; C105905:perifosine; C039128:miltefosine; D000255:Adenosine Triphosphate; D051057:Proto-Oncogene Proteins c-akt
keywords: Leishmania; activity; apoptosis-like; perifosine