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

Abstract

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.

Identification and molecular characterization of the tubulin‐podophyllotoxin‐type lignans binding site on Giardia lamblia

“…A monoclonal anti-α-tubulin antibody revealed that these lignans provoked changes in the distribution and staining pattern of microtubular structures, in a dose-dependent manner (Figure 1). It was associated with a decrease in the polymerized tubulin fraction (Figures 2 and 3); similar results were observed with albendazole, a drug that inhibits microtubule polymerization (Aguayo-Ortiz et al, 2013;Gutiérrez-Gutiérrez, Palomo-Ligas, et al, 2017;Pérez-Rangel et al, 2013). Besides, our results agree with previous findings in mammalian cells, showing that podophyllotoxin-type lignans affect the expression and stability of polymerized tubulin (Kamal et al, 2014;Prinz et al, 2003).…”

Encapsulation of curcumin into layered double hydroxides improve their anticancer and antiparasitic activity

“…A recent work shows that CUR reduces growth in E. histolytica [ 10 ] and in G. lamblia. [ 11,32 ] However, although CUR shows excellent pharmacological qualities, its clinical use is limited, due to the low solubility in water [ 12,13 ] ; thus, limiting their bioavailability and poor systemic absorption in the digestive tract, this promotes poor pharmacokinetics in vivo , which affects their pharmacological effect. [ 14,15 ] Another drawback is that CUR is an unstable molecule, which may suffer degradation by light, [ 6,13,16,18 ] making the pharmacological management difficult.…”

“…[ 8,9 ] Recently, Rangel‐Castañeda and coworkers demonstrated that 100–300 µ m of CUR has amoebicidal activity, affecting Entamoeba histolytica trophozoites, growth, and morphology, in a dose‐dependent behaviour, [ 10 ] in Giardia lamblia CUR inhibits the growth by affecting the microtubules; dramatic changes on cell morphology and loss of attachment were observed. [ 11 ]…”

Antiparasitic Efficacy of Curcumin Against Besnoitia besnoiti Tachyzoites in vitro

“…In addition, in vivo effects of curcumin treatments were also documented in rabbit and sheep coccidiosis (27, 28). Overall, the molecular mechanism of curcumin action is not known so far, but interference with intracellular organelles and cytoskeleton or with cellular metabolism is postulated (29), which might impact on protozoan parasites. Furthermore, curcumin inhibits the glyoxalase system of T. gondii (24) and efficiently blocks histone deacetylation in curcumin-exposed P. falciparum (25).…”