Possible mechanism of miltefosine-mediated death of Leishmania donovani.
Miltefosine causes leishmanial death, but the possible mechanism(s) of action is not known. The mode of action of miltefosine was investigated in vitro in Leishmania donovani promastigotes as well as in extra- and intracellular amastigotes. Here, we demonstrate that miltefosine induces apoptosis-like death in L. donovani based on observed phenomena such as nuclear DNA condensation, DNA fragmentation with accompanying ladder formation, and in situ labeling of DNA fragments by the terminal deoxyribonucleotidyltransferase-mediated dUTP-biotin nick end labeling method. Understanding of miltefosine-mediated death will facilitate the design of new therapeutic strategies against Leishmania parasites.
Department of Biotechnology, National Institute of Pharmaceutical Education and Research, Punjab, India.
Navin K
NK
Verma
Chinmoy S
CS
Dey
D000818:Animals; D000981:Antiprotozoal Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004396:Coloring Agents; D006224:Cricetinae; D003412:Cricetulus; D053938:DNA Fragmentation / Q000187:drug effects; D016054:DNA, Protozoan / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics; D020287:In Situ Nick-End Labeling; D007202:Indicators and Reagents; D007893:Leishmania donovani / Q000187:drug effects* / Q000254:growth & development / Q000648:ultrastructure; D007898:Leishmaniasis, Visceral / Q000188:drug therapy / Q000469:parasitology; D008264:Macrophages / Q000187:drug effects / Q000469:parasitology; D009707:Nucleosomes / Q000187:drug effects / Q000648:ultrastructure; D010767:Phosphorylcholine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011419:Propidium; D013778:Tetrazolium Salts; D013844:Thiazoles
D000981:Antiprotozoal Agents; D004396:Coloring Agents; D016054:DNA, Protozoan; D007202:Indicators and Reagents; D009707:Nucleosomes; D013778:Tetrazolium Salts; D013844:Thiazoles; D010767:Phosphorylcholine; D011419:Propidium; C039128:miltefosine; D011065:Poly(ADP-ribose) Polymerases; C022616:thiazolyl blue