Artemisinin triggers induction of cell-cycle arrest and apoptosis in Leishmania donovani promastigotes.
Sen, Rupashree 1; Bandyopadhyay, Samiran 2; Dutta, Avijit 1; Mandal, Goutam 1; Ganguly, Sudipto 1; Saha, Piu 1; Chatterjee, Mitali 1
Journal of Medical Microbiology.
56(9):1213-1218, September 2007.
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A major impediment to effective anti-leishmanial chemotherapy is the emergence of drug resistance, especially to sodium antimony gluconate, the first-line treatment for leishmaniasis. Artemisinin, a sesquiterpene lactone isolated from Artemisia annua, is an established anti-malarial compound that showed anti-leishmanial activity in both promastigotes and amastigotes, with IC50 values of 160 and 22 [mu]M, respectively, and, importantly, was accompanied by a high safety index (>22-fold). The leishmanicidal activity of artemisinin was mediated via apoptosis as evidenced by externalization of phosphatidylserine, loss of mitochondrial membrane potential, in situ labelling of DNA fragments by terminal deoxyribonucleotidyltransferase-mediated dUTP nick end labelling (TUNEL) and cell-cycle arrest at the sub-G0/G1 phase. Taken together, these data indicate that artemisinin has promising anti-leishmanial activity that is mediated by programmed cell death and, accordingly, merits consideration and further investigation as a therapeutic option for the treatment of leishmaniasis.
Copyright (C) 2007 Society for General Microbiology