Compounds binding to cytoskeletal proteins are active against

Dieckmann-Schuppert, Angela; Franklin, Richard M.

doi:10.1016/0309-1651(89)90135-5

Cited by 32 publications

(9 citation statements)

References 10 publications

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“…Using a trans-well membrane system it was subsequently shown that the transfer of drug resistance is not dependent on cell to cell contact, but instead depends on soluble factors from iRBCs smaller than 400 nm [74]. The transfer is inhibited by cytochalasin D, an inhibitor of actin polymerization and oryzalin [75]. Finally, the transfer of DNA was demonstrated by using in vitro purified EVs.…”

Section: Rbc-derived Evs In Cell-to-cell Communicationmentioning

confidence: 99%

Uncovering the Role of Erythrocyte-Derived Extracellular Vesicles in Malaria: From Immune Regulation to Cell Communication

Ankarklev

Hjelmqvist

Mantel

2014

Journal of Circulating Biomarkers

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Investigation of the involvement of extracellular vesicles (EVs) in parasite biology has burgeoned in recent years. Human infecting protozoan parasites, such as Trypanosoma cruzi, Lesihmania sp. and Trichomonas vaginalis, have all demonstrated the utilization of EVs as virulence factors in order to activate or hamper host immunity. Novel findings have provided evidence that the deployment of EVs by Plasmodium sp. has a major impact in disease outcomes and serves as an integral part in controlling stage switching in its life cycle. Clinical studies have highlighted elevated levels of EVs in patients with severe malaria disease and EVs have been linked to increased sequestration of infected red blood cells to the endothelium, causing obstruction of blood flow. It has also been found that EVs produced during malaria disease activate innate immunity. Intriguingly, recent discoveries indicate that Plasmodium sp. "highjack" the erythrocyte microvesiculation system in order to cross-communicate. Both the transfer of DNA and parasite density regulation has been suggested as key mechanisms of EVs in malaria biology.

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Section: Rbc-derived Evs In Cell-to-cell Communicationmentioning

confidence: 99%

Uncovering the Role of Erythrocyte-Derived Extracellular Vesicles in Malaria: From Immune Regulation to Cell Communication

Ankarklev

Hjelmqvist

Mantel

2014

Journal of Circulating Biomarkers

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“…These include microtubule stabilizing agents - taxoids [22], [23] and various destabilizing agents - colchicum alkaloids [24], [25], vinca alkaloids [26], dinitroanilines [27] and tubulozoles [28], [29]. The effects of microtubule inhibition by these compounds on the erythrocytic cycle of P. falciparum have been suggested due to defects in cellular processes that are thought to be dependent on microtubule function: merozoite formation [23], inhibition of invasion of erythrocytes by daughter merozoites [25] and blocking of nuclear division [22].…”

Section: Introductionmentioning

confidence: 99%

Cellular Effects of Curcumin on Plasmodium falciparum Include Disruption of Microtubules

et al. 2013

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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.

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“…Ultrastructural studies on mitotic spindle formation have only been conducted on sporogony (22) and hepatic schizogony (12). However, a recent immunofluorescence study has described the microtubular organization during the erythrocytic schizogony of P. falciparum (17), and studies with antimicrotubular drugs have pinpointed the essential role of microtubules during asexual schizogony (5,27).…”

mentioning

confidence: 99%

In vitro and in vivo inhibition of erythrocytic development of malarial parasites by docetaxel

Sinou¹,

Grellier²,

Schrével³

1996

Antimicrob Agents Chemother

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The stage-dependent susceptibility of Plasmodium falciparum to a short exposure to docetaxel (Taxotere) was evaluated by subjecting ring-infected, trophozoite-infected, and schizont-infected erythrocytes to a 5-h exposure to various concentrations of the drug. The schizont stage was shown to be the most sensitive stage; an inhibition of more than 60% of parasite development was observed at 10 nM. At this drug concentration, the development of the younger ring and trophozoite forms was unaffected. The in vivo antimalarial activity of docetaxel against the development in blood of old trophozoites of a species that causes malaria in rodents, Plasmodium vinckei petteri, was evaluated in IOPS-OF1 mice. Two tests were performed: the 4-day suppressive test, as described by Peters (W. Peters, p. 145-273, in Chemotherapy, and Drug Resistance in Malaria, vol. 1, 1987), and the effects of a single injection of docetaxel after inoculation of the parasites. A single injection of docetaxel at 40 mg/kg of body weight was sufficient to reduce drastically the level of parasitemia; 90% inhibition of the development of parasites in blood was observed 5 days after drug injection. This program avoided the toxicity observed when mice were treated with four injections of docetaxel. The possibility of using a single bolus of taxoids to treat malaria infections is discussed.

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Compounds binding to cytoskeletal proteins are active against

Cited by 32 publications

References 10 publications

Uncovering the Role of Erythrocyte-Derived Extracellular Vesicles in Malaria: From Immune Regulation to Cell Communication

Uncovering the Role of Erythrocyte-Derived Extracellular Vesicles in Malaria: From Immune Regulation to Cell Communication

Cellular Effects of Curcumin on Plasmodium falciparum Include Disruption of Microtubules

In vitro and in vivo inhibition of erythrocytic development of malarial parasites by docetaxel

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