Artemisinin triggers induction of cell-cycle arrest and apoptosis in Leishmania donovani promastigotes

1 Department of Pharmacology, Institute of Postgraduate Medical Education & Research, 244 B Acharya J. C. Bose Road, Kolkata 700 020, India 2 National Research Centre on Yak, Indian Council of Agricultural Research, Dirang, Arunachal Pradesh 790101, India Correspondence Mitali Chatterjee ilatim{at}vsnl.net Received 26 April 2007 Accepted 22 May 2007 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 IC 50 values of 160 and 22 µM, 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-G 0 /G 1 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. Abbreviations: MTS, 3-(4, 5-dimethylthiazol-2-yl)-5-(3-carboxymethaloxyphenyl)-2-(4-sulfonyl)-2H-tetrazolium inner salt; PI, propidium iodide; TdT, terminal deoxynucleotidyl transferase; TUNEL, TdT-mediated dUTP nick end labelling.