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Updated: May 26, 2026
Deciphering the Molecular Mechanism and Function of Pore-Forming Toxins Using Leishmania major
Published on: October 28, 2022
Miltefosine induces metacaspase and PARP genes expression in Leishmania infantum
Shahram Khademvatan1, Mohammad Javad Gharavi, Jasem Saki
1Department of Medical Parasitology, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
Objectives:
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.
Materials And 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.
Insights
Miltefosine induces programmed cell death (PCD) in Leishmania infantum parasites. This study observed apoptosis-like features and increased metacaspase and PARP gene expression after treatment.
Area of Science:
- Parasitology
- Molecular Biology
- Cell Biology
Background:
- Programmed cell death (PCD) is crucial in multicellular organisms.
- Caspase-related proteases, like metacaspase, are present in protozoan parasites.
- The role of PCD pathways in parasites like Leishmania infantum is an area of active research.
Purpose of the Study:
- To investigate the mechanism of action of miltefosine against Leishmania infantum.
- To analyze the involvement of metacaspase and PARP genes in miltefosine-induced cell death.
- To determine if miltefosine triggers apoptosis in Leishmania infantum.
Main Methods:
- Leishmania infantum promastigotes were treated with varying concentrations of miltefosine.
- Cell viability was assessed using MTT assay.
- Apoptosis was evaluated through Annexin-V FLUOS staining and FACS flow cytometry.
- Metacaspase and PARP gene expression levels were analyzed post-treatment.
Main Results:
- Miltefosine demonstrated a dose-dependent cytotoxic effect on Leishmania infantum.
- The observed cell death exhibited characteristics consistent with apoptosis.
- Overexpression of metacaspase and PARP genes was detected 6 hours after miltefosine treatment.
Conclusions:
- Miltefosine effectively kills Leishmania infantum through an apoptosis-related pathway.
- Metacaspase and PARP gene activation are associated with miltefosine's cytotoxic action.
- This finding contributes to understanding antiparasitic drug mechanisms.
