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 mu M and IC50 after 48 hours of incubation was 7 mu M. Conclusion: Miltefosine exerts cytotoxic effect on Iranian strain of L. infantum via an apoptosis-related mechanism.