Induction of apoptosis by miltefosine in Iranian strain of Leishmania infantum promastigotes

ABSTRACT

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