induction of apoptosis by miltefosine in iranian strain of leishmania infantum promastigotes

background : miltefosine is a new drug of choice for the treatment of visceral leishmaniasis. numerous experi­mental studies have shown miltefosine is effective on leishmania donovani , however, effectiveness of miltefos­ine in treatment of l. infantum is not fully understood. the aims of the present study were to evaluate cytotoxic effects of miltefosine on iranian strain of l. infantum , and to determine its 50% inhibitory concentration (ic50) as well as lethal dose. methods : anti- l. infantum activity of miltefosine was studied by treatment of cultured promastigotes with vari­ous concentration of miltefosine. mtt assay was used to determine l. infantum viability and the results were expressed as ic50. annexin-v fluos staining was performed to study apoptotic properties of this drug by us­ing facs flow cytometry. results : miltefosine led to dose-dependent death of l. infantum with features compatible with apoptosis includ­ing cell shrinkage, dna laddering, and externalization of phosphatidylserine with preservation of integrity of plasma membrane . the 100% effect was achieved at 22 µm and ic50 after 48 hours of incubation was 7 μm. conclusion : miltefosine exerts cytotoxic effect on iranian strain of l. infantum via an apoptosis-related mecha­nism.