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Reactive oxygen species and imbalance of calcium homeostasis contributes to curcumin induced programmed cell death in Leishmania donovani

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Abstract

Curcumin, a polyphenol compound, has been recognized as a promising anti-cancer drug. The purpose of the present study was to investigate the cytotoxicity of curcumin to Leishmania donovani, the causative agent for visceral leishmaniasis. Flow cytometric analysis revealed that curcumin induced cell cycle arrest at G2/M phase. Incubation of Leishmania promastigotes with curcumin caused exposure of phosphatidylserine to the outer leaflet of plasma membrane. This event is preceded by curcumin-induced formation of reactive oxygen species (ROS) and elevation of cytosolic calcium through the release of calcium ions from intracellular stores as well as by influx of extracellular calcium. Elevation of cytosolic calcium is responsible for depolarization of mitochondrial membrane potential (ΔΨm), release of Cytochrome c into the cytosol and concomitant nuclear alterations that included deoxynucleotidyltransferase-mediated dUTP end labeling (TUNEL) and DNA fragmentation. Taken together, these data indicate that curcumin has promising antileishmanial activity that is mediated by programmed cell death and, accordingly, merits further investigation as a therapeutic option for the treatment of leishmaniasis.

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Abbreviations

SR:

Sarcoplasmic reticulum

ROS:

Reactive oxygen species

PI:

Propidium iodide

NAC:

N-acetyl-cysteine

DMSO:

dimethyl sulfoxide

TUNEL:

Terminal deoxynucleotidyltransferase enzyme-mediated dUTP end labeling

HU:

Hydroxyurea

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Acknowledgements

We thank Prof. S. Roy, the Director of our institute, for his interest in this work. We thank Dr. G. Tripathi for her help regarding the confocal microscopic work. This work was supported by the grants from Network Project NWP-0038 Council for Scientific and Industrial Research (CSIR), Government of India to HKM. R.D. was supported by Senior Research Fellowship from CSIR, Government of India.

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  1. Department of Molecular Parasitology, Indian Institute of Chemical Biology, 4, Raja S.C. Mullick Road, Jadavpur, Kolkata, 700032, India

    Rakhee Das, Amit Roy, Neeta Dutta & Hemanta K. Majumder

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  1. Rakhee Das
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  2. Amit Roy
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  4. Hemanta K. Majumder
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Correspondence to Hemanta K. Majumder.

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Das, R., Roy, A., Dutta, N. et al. Reactive oxygen species and imbalance of calcium homeostasis contributes to curcumin induced programmed cell death in Leishmania donovani . Apoptosis 13, 867–882 (2008). https://doi.org/10.1007/s10495-008-0224-7

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