Curcumin alters the cytoskeleton and microtubule organization on trophozoites of Giardia lamblia

[Display omitted] •Curcumin has demonstrated a cytotoxic effect on Giardia lamblia, however, its mechanism of action is still unknown.•Curcumin disrupt the cytoskeletal structures of G. lamblia, it correlates with a reduction of tubulin expression and changes on its distribution.•In this study, we e...

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Published in:Acta tropica 2017-08, Vol.172, p.113-121
Main Authors: Gutiérrez-Gutiérrez, Filiberto, Palomo-Ligas, Lissethe, Hernández-Hernández, José Manuel, Pérez-Rangel, Armando, Aguayo-Ortiz, Rodrigo, Hernández-Campos, Alicia, Castillo, Rafael, González-Pozos, Sirenia, Cortés-Zárate, Rafael, Ramírez-Herrera, Mario Alberto, Mendoza-Magaña, María Luisa, Castillo-Romero, Araceli
Format: Article
Language:English
Subjects:
Animals
Curcumin
Curcumin - pharmacology
Cytoskeleton
Flagella
Giardia lamblia
Giardia lamblia - drug effects
Microscopy, Electron, Scanning
Microtubules
Microtubules - physiology
Parasite
Trophozoites - cytology
Trophozoites - drug effects
Tubulin
Tubulin - metabolism
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Summary:[Display omitted] •Curcumin has demonstrated a cytotoxic effect on Giardia lamblia, however, its mechanism of action is still unknown.•Curcumin disrupt the cytoskeletal structures of G. lamblia, it correlates with a reduction of tubulin expression and changes on its distribution.•In this study, we evaluate tubulin as a target of curcumin in trophozoites of Giardia lamblia.•Curcumin disrupt the cytoskeletal structures of G. lamblia, it correlates with a reduction of tubulin expression and changes on its distribution.•This study is the first evaluate tubulin as a target of curcumin in trophozoites of Giardia lamblia. Giardia lamblia is a worldwide protozoan responsible for a significant number of intestinal infections. There are several drugs for the treatment of giardiasis, but they often cause side effects. Curcumin, a component of turmeric, has antigiardial activity; however, the molecular target and mechanism of antiproliferative activity are not clear. The effects of curcumin on cellular microtubules have been widely investigated. Since tubulin is the most abundant protein in the cytoskeleton of Giardia, to elucidate whether curcumin has activity against the microtubules of this parasite, we treated trophozoites with curcumin and the cells were analyzed by scanning electron microscopy and confocal microscopy. Curcumin inhibited Giardia proliferation and adhesion in a time-concentration-dependent mode. The higher inhibitory concentrations of curcumin (3 and 15μM) disrupted the cytoskeletal structures of trophozoites; the damage was evident on the ventral disk, flagella and in the caudal region, also the membrane was affected. The immunofluorescence images showed altered distribution of tubulin staining on ventral disk and flagella. Additionally, we found that curcumin caused a clear reduction of tubulin expression. By docking analysis and molecular dynamics we showed that curcumin has a high probability to bind at the interface of the tubulin dimer close to the vinblastine binding site. All the data presented indicate that curcumin may inhibit Giardia proliferation by perturbing microtubules.
ISSN:0001-706X
1873-6254
DOI:10.1016/j.actatropica.2017.04.027