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

Abstract

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 microM, 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.

• Authors: Rupashree Sen, Samiran Bandyopadhyay, Avijit Dutta, Goutam Mandal, Sudipto Ganguly, Piu Saha, Mitali Chatterjee
• Journal: Journal of medical microbiology (J Med Microbiol) Vol. 56 Issue Pt 9 Pg. 1213-1218 (Sep 2007) ISSN: 0022-2615 [Print] England
• PMID: 17761485 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antiprotozoal Agents
• Artemisinins
• Phosphatidylserines
• artemisinin

Topics

• Animals
• Antiprotozoal Agents (pharmacology)
• Apoptosis
• Artemisinins (pharmacology)
• Cell Cycle (drug effects)
• Cell Membrane (chemistry)
• DNA Breaks, Single-Stranded
• Humans
• In Situ Nick-End Labeling
• Inhibitory Concentration 50
• Leishmania donovani (cytology, drug effects)
• Membrane Potential, Mitochondrial (drug effects)
• Phosphatidylserines (analysis)