Miltefosine induces metacaspase and PARP genes expression in Leishmania infantum.
OBJECTIVE
Apoptosis is the process of programmed cell death (PCD) that occurs in both animal and plant cells. Protozoan parasites possess metacaspase and these caspase-related proteases could be involved in the PCD pathways in these organisms. Therefore we analyzed the activities of metacaspase and PARP genes in Leishmania infantum (MCAN/IR/96/LON49) treated with miltefosine.


METHODS
Anti-leishmania activity of miltefosine was studied by treatment of cultured promastigotes with various concentration of miltefosine. MTT assay and Annexin-V FLUOS staining by using FACS flow cytometry methods were used. Cytotoxic potential of HePC on the amastigots of L.infantum was evaluated in J774 cell line. In addition, metacaspase and PARP genes expression of treated L. infantum were studied.


RESULTS
Miltefosine led to dose-dependent death of L. infantum with features compatible with apoptosis. Over expression of metacaspase and PARP was seen 6 hr after treatment.


CONCLUSIONS
Our study showed that miltefosine exerts cytotoxic effect on L. infantum via an apoptotic-related mechanism.
Department of Medical Parasitology, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
Shahram
S
Khademvatan
Mohammad Javad
MJ
Gharavi
Jasem
J
Saki
D000981:Antiprotozoal Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D020169:Caspases / Q000187:drug effects* / Q000235:genetics; D003124:Colorimetry; D005434:Flow Cytometry; D005562:Formazans / Q000378:metabolism; D018314:Leishmania infantum / Q000166:cytology / Q000187:drug effects* / Q000235:genetics; D010767:Phosphorylcholine / Q000031:analogs & derivatives* / Q000494:pharmacology; D011065:Poly(ADP-ribose) Polymerases / Q000187:drug effects* / Q000235:genetics; D016133:Polymerase Chain Reaction; D013778:Tetrazolium Salts / Q000378:metabolism
D000981:Antiprotozoal Agents; D005562:Formazans; D013778:Tetrazolium Salts; D010767:Phosphorylcholine; C079782:MTT formazan; C039128:miltefosine; D011065:Poly(ADP-ribose) Polymerases; D020169:Caspases