Record Details

Cellular Effects of Curcumin on Plasmodium falciparum Include Disruption of Microtubules

DSpace at IIT Bombay

View Archive Info
 
 
Field Value
 
Title Cellular Effects of Curcumin on Plasmodium falciparum Include Disruption of Microtubules
 
Creator CHAKRABARTI, R
RAWAT, PS
COOKE, BM
COPPEL, RL
PATANKAR, S
 
Subject NF-KAPPA-B
IN-VITRO
ERYTHROCYTIC DEVELOPMENT
COLCHICINE-BINDING
ENDOTHELIAL-CELLS
MALARIA
INHIBITION
TUBULIN
EXPRESSION
LOCALIZATION
 
Description Curcumin has been widely investigated for its myriad cellular effects resulting in reduced proliferation of various eukaryotic cells including cancer cells and the human malaria parasite Plasmodium falciparum. Studies with human cancer cell lines HT-29, Caco-2, and MCF-7 suggest that curcumin can bind to tubulin and induce alterations in microtubule structure. Based on this finding, we investigated whether curcumin has any effect on P. falciparum microtubules, considering that mammalian and parasite tubulin are 83% identical. IC50 of curcumin was found to be 5 mu M as compared to 20 mu M reported before. Immunofluorescence images of parasites treated with 5 or 20 mu M curcumin showed a concentration-dependent effect on parasite microtubules resulting in diffuse staining contrasting with the discrete hemispindles and subpellicular microtubules observed in untreated parasites. The effect on P. falciparum microtubules was evident only in the second cycle for both concentrations tested. This diffuse pattern of tubulin fluorescence in curcumin treated parasites was similar to the effect of a microtubule destabilizing drug vinblastine on P. falciparum. Molecular docking predicted the binding site of curcumin at the interface of alpha and beta tubulin, similar to another destabilizing drug colchicine. Data from predicted drug binding is supported by results from drug combination assays showing antagonistic interactions between curcumin and colchicine, sharing a similar binding site, and additive/synergistic interactions of curcumin with paclitaxel and vinblastine, having different binding sites. This evidence suggests that cellular effects of curcumin are at least, in part, due to its perturbing effect on P. falciparum microtubules. The action of curcumin, both direct and indirect, on P. falciparum microtubules is discussed.
 
Publisher PUBLIC LIBRARY SCIENCE
 
Date 2014-10-17T04:18:54Z
2014-10-17T04:18:54Z
2013
 
Type Article
 
Identifier PLOS ONE, 8(3)
http://dx.doi.org/10.1371/journal.pone.0057302
http://dspace.library.iitb.ac.in/jspui/handle/100/15930
 
Language en