Cellular effects of curcumin on Plasmodium falciparum include disruption of microtubules.

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 bi...

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Autores principales:	Rimi Chakrabarti, Parkash S Rawat, Brian M Cooke, Ross L Coppel, Swati Patankar
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a2b19257bcdb4de6bbdfe448e35384a8
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spelling	oai:doaj.org-article:a2b19257bcdb4de6bbdfe448e35384a82021-11-18T07:54:28ZCellular effects of curcumin on Plasmodium falciparum include disruption of microtubules.1932-620310.1371/journal.pone.0057302https://doaj.org/article/a2b19257bcdb4de6bbdfe448e35384a82013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23505424/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Curcumin 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 µM as compared to 20 µM reported before. Immunofluorescence images of parasites treated with 5 or 20 µM 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.Rimi ChakrabartiParkash S RawatBrian M CookeRoss L CoppelSwati PatankarPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 3, p e57302 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Rimi Chakrabarti Parkash S Rawat Brian M Cooke Ross L Coppel Swati Patankar Cellular effects of curcumin on Plasmodium falciparum include disruption of microtubules.
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 µM as compared to 20 µM reported before. Immunofluorescence images of parasites treated with 5 or 20 µM 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.
format	article
author	Rimi Chakrabarti Parkash S Rawat Brian M Cooke Ross L Coppel Swati Patankar
author_facet	Rimi Chakrabarti Parkash S Rawat Brian M Cooke Ross L Coppel Swati Patankar
author_sort	Rimi Chakrabarti
title	Cellular effects of curcumin on Plasmodium falciparum include disruption of microtubules.
title_short	Cellular effects of curcumin on Plasmodium falciparum include disruption of microtubules.
title_full	Cellular effects of curcumin on Plasmodium falciparum include disruption of microtubules.
title_fullStr	Cellular effects of curcumin on Plasmodium falciparum include disruption of microtubules.
title_full_unstemmed	Cellular effects of curcumin on Plasmodium falciparum include disruption of microtubules.
title_sort	cellular effects of curcumin on plasmodium falciparum include disruption of microtubules.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/a2b19257bcdb4de6bbdfe448e35384a8
work_keys_str_mv	AT rimichakrabarti cellulareffectsofcurcuminonplasmodiumfalciparumincludedisruptionofmicrotubules AT parkashsrawat cellulareffectsofcurcuminonplasmodiumfalciparumincludedisruptionofmicrotubules AT brianmcooke cellulareffectsofcurcuminonplasmodiumfalciparumincludedisruptionofmicrotubules AT rosslcoppel cellulareffectsofcurcuminonplasmodiumfalciparumincludedisruptionofmicrotubules AT swatipatankar cellulareffectsofcurcuminonplasmodiumfalciparumincludedisruptionofmicrotubules
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Cellular effects of curcumin on Plasmodium falciparum include disruption of microtubules.

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