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Possible Mechanism of Miltefosine-Mediated Death of Leishmania donovani

Department of Biotechnology, National Institute of Pharmaceutical Education and Research (NIPER), Punjab, India¹

Received 10 February 2004/ Returned for modification 29 March 2004/ Accepted 5 April 2004

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.

NIPER communication no. 288.

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