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 ?M and 11 ?M for L. major and L. tropica after 48 hr of incubation, respectively. ED50 of L. major and L. tropica amastigotes were 5.7 ?M and 4.2 ?M, 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.
Citations
Citations to this article as recorded by
Miltefosine reduces coxsackievirus B3 lethality of mice with enhanced STAT3 activation Chun Yu Zhang, Cheng-Huei Hung, Yi-Ling Hsiao, Tung-Miao Chang, Yu-Chieh Su, Li-Chiu Wang, Shih-Min Wang, Shun-Hua Chen Antiviral Research.2024; 223: 105824. CrossRef
Appraisal of Chitosan-Coated Lipid Nano-Combination with Miltefosine and Albendazole in the Treatment of Murine Trichinellosis: Experimental Study with Evaluation of Immunological and Immunohistochemical Parameters Asmaa F. Ibrahim, Sahar M. Selim, Dalia A. Shafey, Dina M. Sweed, Shaimaa A. Farag, Marwa A. Gouda Acta Parasitologica.2024; 69(1): 929. CrossRef
Successful treatment of complex cutaneous leishmaniasis (L. tropica) in a 3‐year‐old Syrian boy with miltefosine Linda Golle, Cord Sunderkötter, Jovine Ehrenreich, Johannes Wohlrab JDDG: Journal der Deutschen Dermatologischen Gesellschaft.2024; 22(8): 1153. CrossRef
Erfolgreiche Therapie einer komplexen kutanen Leishmaniose (L. tropica) bei einem 3‐jährigen syrischen Jungen mit Miltefosin Linda Golle, Cord Sunderkötter, Jovine Ehrenreich, Johannes Wohlrab JDDG: Journal der Deutschen Dermatologischen Gesellschaft.2024; 22(8): 1153. CrossRef
Miltefosine induces reproductive toxicity during sperm capacitation by altering PI3K/AKT signaling pathway Eun-Ju Jung, Woo-Jin Lee, Jeong-Won Bae, Woo-Sung Kwon Environmental Toxicology and Pharmacology.2024; 111: 104565. CrossRef
Anti-leishmanial activity of Hypericum Scabrum extract against Leishmania major Reza Saberi, Zaynab Jamshidzad, Elaheh Karimi, Jahangir Abdi, Razi Naserifar, Asad Mirzaei AMB Express.2024;[Epub] CrossRef
A short-term method to evaluate anti-leishmania drugs by inhibition of stage differentiation in Leishmania mexicana using flow cytometry Christian Florian Teh-Poot, Victor Manuel Dzul-Huchim, Jonathan M. Mercado, Liliana Estefanía Villanueva-Lizama, Maria Elena Bottazzi, Kathryn M. Jones, Francis T.F. Tsai, Julio Vladimir Cruz-Chan Experimental Parasitology.2023; 249: 108519. CrossRef
The Antileishmanial Activity of Eugenol Associated with Lipid Storage Reduction Rather Than Membrane Properties Alterations Kristelle Hughes, Thanh Binh Le, Patrick Van Der Smissen, Donatienne Tyteca, Marie-Paule Mingeot-Leclercq, Joëlle Quetin-Leclercq Molecules.2023; 28(9): 3871. CrossRef
Laurequinone, a Lead Compound against Leishmania Sara García-Davis, Atteneri López-Arencibia, Carlos J. Bethencourt-Estrella, Desirée San Nicolás-Hernández, Ezequiel Viveros-Valdez, Ana R. Díaz-Marrero, José J. Fernández, Jacob Lorenzo-Morales, José E. Piñero Marine Drugs.2023; 21(6): 333. CrossRef
In vitro efficacy of polymer coated miltefosine drug against leishmania tropica Mehvish Khokhar, Muhammad Adnan Shereen, Momin Khan, Rahat Ullah Khan, Aamir Sohail, Imdad Ullah Khan, Inam Ullah Khan, Saadullah Khattak Journal of Parasitic Diseases.2022; 46(2): 366. CrossRef
Tackling Drug Resistance and Other Causes of Treatment Failure in Leishmaniasis Gert-Jan Wijnant, Franck Dumetz, Laura Dirkx, Dimitri Bulté, Bart Cuypers, Katrien Van Bocxlaer, Sarah Hendrickx Frontiers in Tropical Diseases.2022;[Epub] CrossRef
The Effect of Curcumin on the Expression of INFγ, TNF-α, and iNOS
Genes in PBMCs Infected with Leishmania major [MRHO/IR/75/ER] Soheila Alinejad, Shahram Khademvatan, Shahla Amani, Negar Asadi, Khosrow Hazrati Tappeh, Elham Yousefi, Touraj Miandoabi Infectious Disorders - Drug Targets.2022;[Epub] CrossRef
In Vitro Study of Cytotoxic Mechanisms of Alkylphospholipids and Alkyltriazoles in Acute Lymphoblastic Leukemia Models Larissa de Oliveira Passos Jesus, Aline Aparecida de Souza, Heron Fernandes Vieira Torquato, Vanessa Silva Gontijo, Rossimirian Pereira de Freitas, Tarsis Ferreira Gesteira, Vivien Jane Coulson-Thomas, Ricardo José Soares Torquato, Aparecida Sadae Tanaka, Molecules.2022; 27(23): 8633. CrossRef
Anti-leishmanial physalins—Phytochemical investigation, in vitro evaluation against clinical and MIL-resistant L. tropica strains and in silico studies Saira Bano, Memoona Bibi, Saba Farooq, Humaira Zafar, Muniza Shaikh, Behram Khan Khoso, Sammer Yousuf, M. Iqbal Choudhary, Mohammad Shahid PLOS ONE.2022; 17(11): e0274543. CrossRef
Leishmanicidal Activity and Ultrastructural Changes of Maslinic Acid Isolated from Hyptidendron canum Jéssica Adriana Jesus, Márcia Dalastra Laurenti, Matheus Lopes Silva, João Henrique Ghilardi Lago, Luiz Felipe Domingues Passero, Valeria Sülsen Evidence-Based Complementary and Alternative Medicine.2021; 2021: 1. CrossRef
A Novel Automated Framework for QSAR Modeling of Highly Imbalanced Leishmania High-Throughput Screening Data Omar Casanova-Alvarez, Aliuska Morales-Helguera, Miguel Ángel Cabrera-Pérez, Reinaldo Molina-Ruiz, Christophe Molina Journal of Chemical Information and Modeling.2021; 61(7): 3213. CrossRef
Apoptosis-Like Cell Death in Leishmania major Treated with HESA-A: An Herbal Marine Compound Jasem Saki, Khalil Saki, Reza Arjmand Jundishapur Journal of Natural Pharmaceutical Products.2021;[Epub] CrossRef
Une leishmaniose cutanée réfractaire : intérêt de la miltéfosine C. Guerveno, K. Delavigne, A. Berry, G. Martin-Blondel, P. Delobel Médecine et Maladies Infectieuses.2019; 49(4): 281. CrossRef
Natural compounds from plants controlling leishmanial growth via DNA damage and inhibiting trypanothione reductase and trypanothione synthetase: an in vitro and in silico approach Shaila Mehwish, Huma Khan, Ashfaq Ur Rehman, Asif Ullah Khan, Mubarak Ali Khan, Obaid Hayat, Mansoor Ahmad, Abdul Wadood, Nazif Ullah 3 Biotech.2019;[Epub] CrossRef
Antileishmanial and cytotoxic activities of ionic surfactants compared to those of miltefosine Lais Alonso, Éder Jeferson Souza Cardoso, Rodrigo Saar Gomes, Sebastião Antônio Mendanha, Miriam Leandro Dorta, Antonio Alonso Colloids and Surfaces B: Biointerfaces.2019; 183: 110421. CrossRef
In vitro study of the efficacy of Solanum nigrum against Leishmania major Christine N. Mutoro, Johnson K. Kinyua, Joseph K. Ng'ang'a, Daniel W. Kariuki, Johnstone M. Ingonga, Christopher O. Anjili F1000Research.2018; 7: 1329. CrossRef
The cytotoxic activity of miltefosine against Leishmania and macrophages is associated with dynamic changes in plasma membrane proteins Kelly Souza Fernandes, Paulo Eduardo Narcizo de Souza, Miriam Leandro Dorta, Antonio Alonso Biochimica et Biophysica Acta (BBA) - Biomembranes.2017; 1859(1): 1. CrossRef
Antileishmanial and Immunomodulatory Activity of Allium sativum (Garlic) Masoud Foroutan-Rad, Khosrow Hazrati Tappeh, Shahram Khademvatan Journal of Evidence-Based Complementary & Alternative Medicine.2017; 22(1): 141. CrossRef
Effect of 1,2,3-triazole salts, non-classical bioisosteres of miltefosine, on Leishmania amazonensis Pedro H.F. Stroppa, Luciana M.R. Antinarelli, Arturene M.L. Carmo, Jacy Gameiro, Elaine S. Coimbra, Adilson D. da Silva Bioorganic & Medicinal Chemistry.2017; 25(12): 3034. CrossRef
Pomegranate (Punica granatum) Juice Shows Antioxidant Activity against Cutaneous Leishmaniasis-Induced Oxidative Stress in Female BALB/c Mice Badriah Alkathiri, Manal El-Khadragy, Dina Metwally, Ebtesam Al-Olayan, Muhammed Bakhrebah, Ahmed Abdel Moneim International Journal of Environmental Research and Public Health.2017; 14(12): 1592. CrossRef
Enterocin AS-48 as Evidence for the Use of Bacteriocins as New Leishmanicidal Agents María Ángeles Abengózar, Rubén Cebrián, José María Saugar, Teresa Gárate, Eva Valdivia, Manuel Martínez-Bueno, Mercedes Maqueda, Luis Rivas Antimicrobial Agents and Chemotherapy.2017;[Epub] CrossRef
The antifungal compound butenafine eliminates promastigote and amastigote forms of Leishmania (Leishmania) amazonensis and Leishmania (Viannia) braziliensis Adriana Bezerra-Souza, Eduardo S. Yamamoto, Márcia D. Laurenti, Susan P. Ribeiro, Luiz Felipe D. Passero Parasitology International.2016; 65(6): 702. CrossRef
New Approaches to Overcome Transport Related Drug Resistance in Trypanosomatid Parasites Jose A. Garcia-Salcedo, Juan D. Unciti-Broceta, Javier Valverde-Pozo, Miguel Soriano Frontiers in Pharmacology.2016;[Epub] CrossRef
Molecular docking and molecular dynamics simulation study of inositol phosphorylceramide synthase – inhibitor complex in leishmaniasis: Insight into the structure based drug design Vineetha Mandlik, Shailza Singh F1000Research.2016; 5: 1610. CrossRef
A Telomeric Cluster of Antimony Resistance Genes on Chromosome 34 of Leishmania infantum Paloma Tejera Nevado, Eugenia Bifeld, Katharina Höhn, Joachim Clos Antimicrobial Agents and Chemotherapy.2016; 60(9): 5262. CrossRef
Molecular docking and molecular dynamics simulation study of inositol phosphorylceramide synthase – inhibitor complex in leishmaniasis: Insight into the structure based drug design Vineetha Mandlik, Shailza Singh F1000Research.2016; 5: 1610. CrossRef
Cinnamic Acid Bornyl Ester Derivatives from Valeriana wallichii Exhibit Antileishmanial In Vivo Activity in Leishmania major-Infected BALB/c Mice Anita Masic, Ana Maria Valencia Hernandez, Sudipta Hazra, Jan Glaser, Ulrike Holzgrabe, Banasri Hazra, Uta Schurigt, Bhaskar Saha PLOS ONE.2015; 10(11): e0142386. CrossRef
Evaluation of the effect of miltefosine on Trichomonas vaginalis Débora Afonso Silva Rocha, Ivone de Andrade Rosa, Wanderley de Souza, Marlene Benchimol Parasitology Research.2014; 113(3): 1041. CrossRef
In silico and in vitro comparative activity of novel experimental derivatives against Leishmania major and Leishmania infantum promastigotes Shahram Khademvatan, Neda Adibpour, Alborz Eskandari, Saeed Rezaee, Mahmoud Hashemitabar, Fakher Rahim Experimental Parasitology.2013; 135(2): 208. CrossRef
Pistagremic acid a new leishmanicidal triterpene isolated from Pistacia integerrima Stewart Ghias Uddin, Abdur Rauf, Mohammad Arfan, Waliullah, Inamullah khan, Mumtaz Ali, Mazhar Taimur, Inaayat ur-Rehman, Samiullah Journal of Enzyme Inhibition and Medicinal Chemistry.2012; 27(5): 646. CrossRef
First
Prev
