Colchicine treatment reversibly blocks cytokinesis but not mitosis in Trypanosoma cruzi epimastigotes

Potenza, Mariana; Téllez-Iñón, Marı́a T.

doi:10.1007/s00436-014-4227-8

Cited by 8 publications

(7 citation statements)

References 49 publications

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“…The negative effects of solenopsins on the proliferation of T. cruzi epimastigote forms were reversible, similar to previous reports on other alkaloids [50][51][52][53][54] . Additionally, the observation that epimastigotes become rounded with increased intracellular vacuolization and complex membrane invaginations has been reported for most studies involving the treatment of T. cruzi with alkaloids.…”

Section: Discussionsupporting

confidence: 89%

“…A remarkable difference herein, however, was the absence of a clear swelling of the mitochondrial matrix, as observed with camptothecin 48,50 or piperine 52 . Additionally, solenopsins delayed cell cycle progression but did not block the synthesis or segregation of nuclear and kinetoplast DNA, as reported with Taxol 50 or colchicine 54 . Finally, unlike the effects caused by vinblastine and vincristine that induce cytokinesis arrest in T. cruzi epimastigotes 51 , exposure to solenopsins did not induce the formation of multinucleate cells.…”

Section: Discussionsupporting

confidence: 64%

“…Concerning histone interactions, it has been shown that the overexpression of histone (H1) in Leishmania generates a delay in the cell cycle from increased histone interactions with nuclear DNA 58 . Chaetocin, a fungal toxin possessing an epipolythiodioxopiperazine alkaloid moiety and a nonspecific inhibitor of histone lysine methyltransferases 59,60 , has been shown to impair proliferation, arrest cell cycle progression and induce nucleolar disassembly in T. cruzi 53 www.nature.com/scientificreports/ post-transcriptional regulatory levels and regulating tubulin expression in T. cruzi 54 . Similar effects could also result from solenopsin alkaloids affecting membrane transporters, as has been already described in mammalian cells 13,17,18 .…”

Section: Discussionmentioning

confidence: 99%

“…The collected evidence indicates that solenopsins act on interconnected pathways. Therefore, it seems worthwhile to explore whether ROS and Ca +2 levels (e.g., in the mitochondria) are also affected by exposure to solenopsins and would further indicate whether the alkaloids can mediate T. cruzi apoptosis 54,76 .…”

Section: Discussionmentioning

confidence: 99%

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Venom alkaloids against Chagas disease parasite: search for effective therapies

Silva

Fox

Gomes

et al. 2020

Sci Rep

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Chagas disease is an important disease affecting millions of patients in the New World and is caused by a protozoan transmitted by haematophagous kissing bugs. It can be treated with drugs during the early acute phase; however, effective therapy against the chronic form of Chagas disease has yet to be discovered and developed. We herein tested the activity of solenopsin alkaloids extracted from two species of fire ants against the protozoan parasite Trypanosoma cruzi, the aetiologic agent of Chagas disease. Although IC 50 determinations showed that solenopsins are more toxic to the parasite than benznidazole, the drug of choice for Chagas disease treatment, the ant alkaloids presented a lower selectivity index. As a result of exposure to the alkaloids, the parasites became swollen and rounded in shape, with hypertrophied contractile vacuoles and intense cytoplasmic vacuolization, possibly resulting in osmotic stress; no accumulation of multiple kinetoplasts and/or nuclei was detected. Overexpressing phosphatidylinositol 3-kinase-an enzyme essential for osmoregulation that is a known target of solenopsins in mammalian cells-did not prevent swelling and vacuolization, nor did it counteract the toxic effects of alkaloids on the parasites. Additional experimental results suggested that solenopsins induced a type of autophagic and programmed cell death in T. cruzi. Solenopsins also reduced the intracellular proliferation of T. cruzi amastigotes in infected macrophages in a concentration-dependent manner and demonstrated activity against Trypanosoma brucei rhodesiense bloodstream forms, which is another important aetiological kinetoplastid parasite. The results suggest the potential of solenopsins as novel natural drugs against neglected parasitic diseases caused by kinetoplastids. Alkaloids are organic compounds containing a nitrogen atom usually associated with the cyclic chain within its structure 1. They are a large, diverse group of chemicals, in which some compounds are known as poisons (e.g., strychnine), stimulants (e.g., caffeine), and analgesics (e.g., morphine) 2. Alkaloids are mostly found in plants but have also been identified from a number of animals, such as frogs and ants 1. Recently, several studies have evaluated the potential of antimicrobial alkaloids as prospective new drugs against diseases caused by bacteria 3

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Section: Discussionsupporting

confidence: 89%

Section: Discussionsupporting

confidence: 64%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Venom alkaloids against Chagas disease parasite: search for effective therapies

Silva

Fox

Gomes

et al. 2020

Sci Rep

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“…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%

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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