Growth arrest and morphological changes triggered by emodin on Trypanosoma cruzi epimastigotes cultivated in axenic medium

Lima, Ana Rita de; Noris-Suárez, Karem; Bretan̄a, Antonio; Contreras, Víctor; Navarro, Marian; Pérez-Ybarra, Luis; Bubis, José

doi:10.1016/j.biochi.2017.08.005

Cited by 8 publications

(7 citation statements)

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“…Further, PfPKG inhibitory thiazole compounds with additional activity against PfCDPK4, PfCRK5, and PfNEK1 have been identified (Penzo et al, 2019), as well as PfCDPK4 inhibitors that block exflagellation and hence, likely, transmission of P. falciparum (Ojo et al, 2014; Vidadala et al, 2014). TgMAPKL-1, targeted by bumped kinase inhibitors, is reported to have promising drug target potential (Sugi et al, 2013, 2015; Brown et al, 2014), TbPK50 and TbPK53 kinase inhibitors have been identified (Ma et al, 2010; Urbaniak et al, 2012) and the CK2 inhibitor, emodin, inhibits cytokinesis in T. cruzi (De Lima et al, 2017). Aside from protein kinases, sphingosine derivatives and inhibitors of sphingolipid biosynthetic enzymes have potential against Giardia (Sonda et al, 2008; Stefanic et al, 2010) and T. brucei (Fridberg et al, 2008; Jones et al, 2015), while repurposing of human PDE inhibitors shows promise in T. brucei (de Koning et al, 2012; Ochiana et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

“…However, while there are additional cytoskeleton components and the order of organelle replication differs in T. cruzi compared to T. brucei (Elias et al, 2007), the overall process of cytokinesis appears similar, with a furrow ingressing from the anterior to the posterior. Little is known about the molecular regulation of T. cruzi cytokinesis, although colchicine, which blocks microtubule polymerization, the protein phosphatase 1 (PP1)-inhibitor, calyculin, and the Casein Kinase 2 (CK2) inhibitor, emodin, inhibit epimastigote cytokinesis (Orr et al, 2000; Potenza and Tellez-Inon, 2015; De Lima et al, 2017). However, T. cruzi AUK1 is apparently not required for cytokinesis (Fassolari and Alonso, 2019).…”

Section: Cytokinesis In the Excavatamentioning

confidence: 99%

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Who Needs a Contractile Actomyosin Ring? The Plethora of Alternative Ways to Divide a Protozoan Parasite

Hammarton

2019

Front. Cell. Infect. Microbiol.

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Cytokinesis, or the division of the cytoplasm, following the end of mitosis or meiosis, is accomplished in animal cells, fungi, and amoebae, by the constriction of an actomyosin contractile ring, comprising filamentous actin, myosin II, and associated proteins. However, despite this being the best-studied mode of cytokinesis, it is restricted to the Opisthokonta and Amoebozoa, since members of other evolutionary supergroups lack myosin II and must, therefore, employ different mechanisms. In particular, parasitic protozoa, many of which cause significant morbidity and mortality in humans and animals as well as considerable economic losses, employ a wide diversity of mechanisms to divide, few, if any, of which involve myosin II. In some cases, cell division is not only myosin II-independent, but actin-independent too. Mechanisms employed range from primitive mechanical cell rupture (cytofission), to motility- and/or microtubule remodeling-dependent mechanisms, to budding involving the constriction of divergent contractile rings, to hijacking host cell division machinery, with some species able to utilize multiple mechanisms. Here, I review current knowledge of cytokinesis mechanisms and their molecular control in mammalian-infective parasitic protozoa from the Excavata, Alveolata, and Amoebozoa supergroups, highlighting their often-underappreciated diversity and complexity. Billions of people and animals across the world are at risk from these pathogens, for which vaccines and/or optimal treatments are often not available. Exploiting the divergent cell division machinery in these parasites may provide new avenues for the treatment of protozoal disease.

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Section: Discussionmentioning

confidence: 99%

Section: Cytokinesis In the Excavatamentioning

confidence: 99%

Who Needs a Contractile Actomyosin Ring? The Plethora of Alternative Ways to Divide a Protozoan Parasite

Hammarton

2019

Front. Cell. Infect. Microbiol.

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“…A. lappa is used as diuretic, depurative, digestive stimulant, and anti-allergic (Soh et al, 2011;De Almeida et al, 2012). R. palmatum contains a natural anthraquinone called emodin that has been reported to inhibit the protein kinase CK2 (Yim, Lee, Lee, & Lee, 1999) and to block cell division of Trypanosoma cruzi epimastigotes in vitro (De Lima et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

Anti-leukemic activity of a four-plant mixture in a leukemic rat model

Kabeel

Ghoneim

Mansy

2018

JoBAZ

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“…In our study, emodin showed specific submicromolar inhibition of parasite release in CHO cells. Emodin was previously only tested on epimastigotes at high micromolar concentrations (94) where it inhibited casein kinase 1 with an IC 50 value of 130 µM (95), thus significantly less potent than in the trypomastigote infection assay shown here. Other reported effects of this natural product include antiinflammatory, antiosteoporosis, and antidepressant effects (93).…”

Section: Sar Study Of Anthraquinones As Antichagasic Natural Productsmentioning

confidence: 82%

Phylobioactive hotspots identified through multidimensional profiling of botanical drugs used to treat Chagas disease in Bolivia and Dioscorides’ De Materia Medica

Salm

Krishnan

Collu

et al. 2019

Preprint

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Globally, more than six million people are infected with Trypanosoma cruzi, the causative protozoan parasite of the vector-borne Chagas disease (CD). In Bolivia, CD is hyperendemic and a major health problem among indigenous communities. Although botanical drugs are used widely among different ethnic groups in Bolivia, studies challenging the hypothesis that effective antitrypanosomal medicinal agents were identified empirically are lacking. We conducted a cross-sectional ethnopharmacological field study in Bolivia among different ethnic groups in the Chaco, Chiquitanía and Inter-Andean valleys. We compared botanical drugs used in Bolivia in the context of CD with botanical drugs from unrelated indications from the Mediterranean De Materia Medica (DMM) compiled by Dioscorides two thousand years ago. A total of 775 ethyl acetate plant extracts with and without ethnomedical indications for CD treatment were profiled against T. cruzi epimastigote and procyclic T. brucei proliferation, parasite release from T. cruzi trypomastigote infected cells, as well as for host cell cytotoxicity in vitro. Inhibition of parasite release was monitored using a flow cytometry-based celluar assay. At 25 µg/mL, less than 5% of all extracts exhibited selective toxicity for T. cruzi. We found no evidence that ethnomedicine-inspired bioprospecting significantly increased the probability of finding selective antichagasic botanical drugs. The ethnomedical data further indicate a discrepancy between local and scientific concepts about CD among the studied ethnic groups. Intriguingly, the phylobioactive anthraquinone hotspot identified in this study matched the antichagasic activity of Senna chloroclada, the taxon with the strongest consensus for treating CD among the Izoceño-Guaraní. Selected antitrypanosomal plant extracts from DMM were subjected to HPLC-based activity profiling and targeted isolation of active compounds yielding sesquiterpene lactones, naphtoquinones and anthraquinones. Because the anthraquinone emodin selectively and potently inhibited T. cruzi in host cell infection, we performed a preliminary structure-activity relationship analysis for the 9,10-anthracenedione scaffold, exploring the impact of differential hydroxylation. This study shows that the multidimensional phylobioactivity-guided identification of antichagasic natural products enables comparative bioprospecting and is suitable to challenge ethnopharmacological hypotheses. Author summaryChagas disease (CD) is a parasitic disease caused by the protozoan Trypanosoma cruzi. In Bolivia, CD is a major health problem among indigenous communities, which frequently use traditional medicine to treat the chronic symptoms of the disease related to cardiomyopathy. However, the ethnomedical context of the use of such remedies is largely unclear and it remains unknown whether the botanical drugs have any effect on parasitemia. In a field study among different ethnic groups in the Chaco, Chiquitanía and Inter-Andean valleys the authors collected ethnobotanical and ethnopharmac...

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Growth arrest and morphological changes triggered by emodin on Trypanosoma cruzi epimastigotes cultivated in axenic medium

Cited by 8 publications

References 47 publications

Who Needs a Contractile Actomyosin Ring? The Plethora of Alternative Ways to Divide a Protozoan Parasite

Who Needs a Contractile Actomyosin Ring? The Plethora of Alternative Ways to Divide a Protozoan Parasite

Anti-leukemic activity of a four-plant mixture in a leukemic rat model

Phylobioactive hotspots identified through multidimensional profiling of botanical drugs used to treat Chagas disease in Bolivia and Dioscorides’ De Materia Medica

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