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Miltefosine-Induced Apoptotic Cell Death on Leishmania major and L. tropica Strains
The aim of this study was to assess the cytotoxic effects of various concentrations of miltefosine on Leishmania major (MRHO/IR/75/ER) and L. tropica (MHOM/IR/02/Mash10) promastigotes and to observe the programmed cell death features. The colorimetric MTT assay was used to find L. major and L. tropi...
Autores principales: | , , , |
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Formato: | Texto |
Lenguaje: | English |
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The Korean Society for Parasitology
2011
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3063921/ https://www.ncbi.nlm.nih.gov/pubmed/21461264 http://dx.doi.org/10.3347/kjp.2011.49.1.17 |
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author | Khademvatan, Shahram Gharavi, Mohammad Javad Rahim, Fakher Saki, Jasem |
author_facet | Khademvatan, Shahram Gharavi, Mohammad Javad Rahim, Fakher Saki, Jasem |
author_sort | Khademvatan, Shahram |
collection | PubMed |
description | The aim of this study was to assess the cytotoxic effects of various concentrations of miltefosine on Leishmania major (MRHO/IR/75/ER) and L. tropica (MHOM/IR/02/Mash10) promastigotes and to observe the programmed cell death features. The colorimetric MTT assay was used to find L. major and L. tropica viability and the obtained results were expressed as 50% inhibitory concentration (IC50). Also, 50% effective doses (ED50) for L. major and L. tropica amastigotes were also determined. Annexin-V FLUOS staining was performed to study the cell death properties of miltefosine using FACS analysis. Qualitative analysis of the total genomic DNA fragmentation was performed by agarose gel electrophoresis. Furthermore, to observe changes in cell morphology, promastigotes were examined using light microscopy. In both strains of L. major and L. tropica, miltefosine induced dose-dependent death with features of apoptosis, including cell shrinkage, DNA laddering, and externalization of phosphatidylserine. The IC50 was achieved at 22 µM and 11 µM for L. major and L. tropica after 48 hr of incubation, respectively. ED50 of L. major and L. tropica amastigotes were 5.7 µM and 4.2 µM, respectively. Our results indicate that miltefosine induces apoptosis of the causative agent of cutaneous leishmaniasis in a dose-dependent manner. Interestingly, L. major did not display any apoptotic changes when it was exposed to miltefosine in concentrations sufficient to kill L. tropica. |
format | Text |
id | pubmed-3063921 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | The Korean Society for Parasitology |
record_format | MEDLINE/PubMed |
spelling | pubmed-30639212011-03-31 Miltefosine-Induced Apoptotic Cell Death on Leishmania major and L. tropica Strains Khademvatan, Shahram Gharavi, Mohammad Javad Rahim, Fakher Saki, Jasem Korean J Parasitol Original Article The aim of this study was to assess the cytotoxic effects of various concentrations of miltefosine on Leishmania major (MRHO/IR/75/ER) and L. tropica (MHOM/IR/02/Mash10) promastigotes and to observe the programmed cell death features. The colorimetric MTT assay was used to find L. major and L. tropica viability and the obtained results were expressed as 50% inhibitory concentration (IC50). Also, 50% effective doses (ED50) for L. major and L. tropica amastigotes were also determined. Annexin-V FLUOS staining was performed to study the cell death properties of miltefosine using FACS analysis. Qualitative analysis of the total genomic DNA fragmentation was performed by agarose gel electrophoresis. Furthermore, to observe changes in cell morphology, promastigotes were examined using light microscopy. In both strains of L. major and L. tropica, miltefosine induced dose-dependent death with features of apoptosis, including cell shrinkage, DNA laddering, and externalization of phosphatidylserine. The IC50 was achieved at 22 µM and 11 µM for L. major and L. tropica after 48 hr of incubation, respectively. ED50 of L. major and L. tropica amastigotes were 5.7 µM and 4.2 µM, respectively. Our results indicate that miltefosine induces apoptosis of the causative agent of cutaneous leishmaniasis in a dose-dependent manner. Interestingly, L. major did not display any apoptotic changes when it was exposed to miltefosine in concentrations sufficient to kill L. tropica. The Korean Society for Parasitology 2011-03 2011-03-18 /pmc/articles/PMC3063921/ /pubmed/21461264 http://dx.doi.org/10.3347/kjp.2011.49.1.17 Text en © 2011, Korean Society for Parasitology http://creativecommons.org/licenses/by-nc/3.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Article Khademvatan, Shahram Gharavi, Mohammad Javad Rahim, Fakher Saki, Jasem Miltefosine-Induced Apoptotic Cell Death on Leishmania major and L. tropica Strains |
title | Miltefosine-Induced Apoptotic Cell Death on Leishmania major and L. tropica Strains |
title_full | Miltefosine-Induced Apoptotic Cell Death on Leishmania major and L. tropica Strains |
title_fullStr | Miltefosine-Induced Apoptotic Cell Death on Leishmania major and L. tropica Strains |
title_full_unstemmed | Miltefosine-Induced Apoptotic Cell Death on Leishmania major and L. tropica Strains |
title_short | Miltefosine-Induced Apoptotic Cell Death on Leishmania major and L. tropica Strains |
title_sort | miltefosine-induced apoptotic cell death on leishmania major and l. tropica strains |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3063921/ https://www.ncbi.nlm.nih.gov/pubmed/21461264 http://dx.doi.org/10.3347/kjp.2011.49.1.17 |
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