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

作者:Sen Rupashree; Bandyopadhyay Samiran; Dutta Avijit; Mandal Goutam; Ganguly Sudipto; Saha Piu; Chatterjee Mitali*
来源:Journal of Medical Microbiology, 2007, 56(9): 1213-1218.
DOI:10.1099/jmm.0.47364-0

摘要

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 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-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.