Aloe vera leaf exudate induces a caspase-independent cell death in Leishmania donovani promastigotes.
Leishmaniasis constitutes a complex of diseases with clinical and epidemiological diversity and includes visceral leishmaniasis, a disease that is fatal when left untreated. In earlier studies, the authors reported that Aloe vera leaf exudate (AVL) is a potent antileishmanial agent effective in promastigotes of Leishmania braziliensis, Leishmania mexicana, Leishmania tropica, Leishmania major and Leishmania infantum and also in axenic amastigotes of Leishmania donovani. In the present study, it has been demonstrated that, in promastigotes of L. donovani (IC(50) = 110 microg ml(-1)), AVL mediates this leishmanicidal effect by triggering a programmed cell death. Incubation of promastigotes with AVL caused translocation of phosphatidylserine to the outer leaflet of the plasma membrane as measured by annexin V binding, which was accompanied by loss of mitochondrial membrane potential, release of cytochrome c into the cytosol and concomitant nuclear alterations that included chromatin condensation, deoxynucleotidyltransferase-mediated dUTP end labelling and DNA laddering. As this AVL-induced leishmanicidal effect could not be inhibited by protease inhibitors including Z-Val-Ala-dl-Asp (methoxy)-fluoromethylketone, a broad-spectrum caspase inhibitor, non-involvement of caspases and major proteases was suggested. Additionally, AVL treatment caused no increase in cytosolic Ca(2+) or generation of reactive oxygen species, indicating that although promastigote death was induced by an apoptotic-like mechanism similar to metazoan apoptosis, the pathways of induction and/or execution differed at the molecular level.
Dutta
Avijit
A
Department of Immunobiology, Indian Institute of Chemical Biology, 4 Raja SC Mullick Road, Kolkata 700 032, India.
Bandyopadhyay
Suman
S
Department of Immunobiology, Indian Institute of Chemical Biology, 4 Raja SC Mullick Road, Kolkata 700 032, India.
Mandal
Chitra
C
Department of Immunobiology, Indian Institute of Chemical Biology, 4 Raja SC Mullick Road, Kolkata 700 032, India.
Chatterjee
Mitali
M
Department of Pharmacology, Institute of Postgraduate Medical Education & Research, 244 B Acharya JC Bose Road, Kolkata 700 020, India.
D000504:Aloe / Q000737:chemistry*; D000818:Animals; D017304:Annexin A5 / Q000378:metabolism; D000981:Antiprotozoal Agents / Q000494:pharmacology*; D017209:Apoptosis; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism; D002462:Cell Membrane / Q000737:chemistry; D045304:Cytochromes c / Q000378:metabolism; D003593:Cytoplasm / Q000737:chemistry; D053938:DNA Fragmentation; D020287:In Situ Nick-End Labeling; D007893:Leishmania donovani / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000502:physiology; D010718:Phosphatidylserines / Q000032:analysis; D010936:Plant Extracts / Q000494:pharmacology*
D017304:Annexin A5; D000981:Antiprotozoal Agents; D061945:Caspase Inhibitors; D010718:Phosphatidylserines; D010936:Plant Extracts; D045304:Cytochromes c; D020169:Caspases