Artemisinin triggers induction of cell-cycle arrest and apoptosis in Leishmania donovani promastigotes.
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.
Sen
Rupashree
R
Department of Pharmacology, Institute of Postgraduate Medical Education & Research, 244 B Acharya J. C. Bose Road, Kolkata 700 020, India.
Bandyopadhyay
Samiran
S
National Research Centre on Yak, Indian Council of Agricultural Research, Dirang, Arunachal Pradesh 790101, India.
Dutta
Avijit
A
Department of Pharmacology, Institute of Postgraduate Medical Education & Research, 244 B Acharya J. C. Bose Road, Kolkata 700 020, India.
Mandal
Goutam
G
Department of Pharmacology, Institute of Postgraduate Medical Education & Research, 244 B Acharya J. C. Bose Road, Kolkata 700 020, India.
Ganguly
Sudipto
S
Department of Pharmacology, Institute of Postgraduate Medical Education & Research, 244 B Acharya J. C. Bose Road, Kolkata 700 020, India.
Saha
Piu
P
Department of Pharmacology, Institute of Postgraduate Medical Education & Research, 244 B Acharya J. C. Bose Road, Kolkata 700 020, India.
Chatterjee
Mitali
M
Department of Pharmacology, Institute of Postgraduate Medical Education & Research, 244 B Acharya J. C. Bose Road, Kolkata 700 020, India.
D000818:Animals; D000981:Antiprotozoal Agents / Q000494:pharmacology*; D017209:Apoptosis; D037621:Artemisinins / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects*; D002462:Cell Membrane / Q000737:chemistry; D053904:DNA Breaks, Single-Stranded; D006801:Humans; D020287:In Situ Nick-End Labeling; D020128:Inhibitory Concentration 50; D007893:Leishmania donovani / Q000166:cytology / Q000187:drug effects*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D010718:Phosphatidylserines / Q000032:analysis
D000981:Antiprotozoal Agents; D037621:Artemisinins; D010718:Phosphatidylserines; C031327:artemisinin