Effects of a novel β-lapachone derivative on Trypanosoma cruzi: Parasite death involving apoptosis, autophagy and necrosis

Detalhes bibliográficos
Autor(a) principal: Anjos, Danielle Oliveira dos
Data de Publicação: 2016
Outros Autores: Alves, Eliomara Sousa Sobral, Gonçalves, Vinicius Tomaz, Fontes, Sheila Suarez, Nogueira, Mateus Lima, Fontes, Ana Márcia Suarez, Costa, João Batista Neves da, Santos, Fabricio Rios, Santos, Marcos André Vannier dos
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/18066
Resumo: CNPq, PROCAD/Capes PP-SUS, PROEP, INCTINPeTAm, FAPESB, PRONEX/MCT.
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spelling Anjos, Danielle Oliveira dosAlves, Eliomara Sousa SobralGonçalves, Vinicius TomazFontes, Sheila SuarezNogueira, Mateus LimaFontes, Ana Márcia SuarezCosta, João Batista Neves daSantos, Fabricio RiosSantos, Marcos André Vannier dos2017-03-16T17:40:58Z2017-03-16T17:40:58Z2016ANJOS, D. O. dos Effects of a novel β-lapachone derivative on Trypanosoma cruzi: Parasite death involving apoptosis, autophagy and necrosis. Drugs and Drug Resistance, v. 6, p. 207e219, 2016.0020-7519https://www.arca.fiocruz.br/handle/icict/1806610.1016/j.ijpddr.2016.10.003CNPq, PROCAD/Capes PP-SUS, PROEP, INCTINPeTAm, FAPESB, PRONEX/MCT.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Biologia Parasitária. Salvador, BA, Brasil / Universidade Estadual de Santa Cruz UESC. Departamento de Ciências Biológicas. Ilhéus, BA, BrasilFundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Biologia Parasitária. Salvador, BA, BrasilUniversidade Federal Rural do Rio de Janeiro. UFRRJ. Instituto de Química. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Biologia Parasitária. Salvador, BA, BrasilFundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Biologia Parasitária. Salvador, BA, BrasilFundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Biologia Parasitária. Salvador, BA, BrasilUniversidade Federal Rural do Rio de Janeiro. UFRRJ. Instituto de Química. Rio de Janeiro, RJ, BrasilUniversidade Federal de Mato Grosso. UFMT. Faculdade de Medicina. Cuiabá, MG, BrasilFundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Biologia Parasitária. Salvador, BA, BrasilNatural products comprise valuable sources for new antiparasitic drugs. Here we tested the effects of a novel β-lapachone derivative on Trypanosoma cruzi parasite survival and proliferation and used microscopy and cytometry techniques to approach the mechanism(s) underlying parasite death. The selectivity index determination indicate that the compound trypanocidal activity was over ten-fold more cytotoxic to epimastigotes than to macrophages or splenocytes. Scanning electron microscopy analysis revealed that the R72 β-lapachone derivative affected the T. cruzi morphology and surface topography. General plasma membrane waving and blebbing particularly on the cytostome region were observed in the R72-treated parasites. Transmission electron microscopy observations confirmed the surface damage at the cytostome opening vicinity. We also observed ultrastructural evidence of the autophagic mechanism termed macroautophagy. Some of the autophagosomes involved large portions of the parasite cytoplasm and their fusion/confluence may lead to necrotic parasite death. The remarkably enhanced frequency of autophagy triggering was confirmed by quantitating monodansylcadaverine labeling. Some cells displayed evidence of chromatin pycnosis and nuclear fragmentation were detected. This latter phenomenon was also indicated by DAPI staining of R72-treated cells. The apoptotis induction was suggested to take place in circa one-third of the parasites assessed by annexin V labeling measured by flow cytometry. TUNEL staining corroborated the apoptosis induction. Propidium iodide labeling indicate that at least 10% of the R72-treated parasites suffered necrosis within 24 h. The present data indicate that the β-lapachone derivative R72 selectively triggers T. cruzi cell death, involving both apoptosis and autophagy-induced necrosis.engElsevierTrypanosoma cruziDoença de ChagasQuimioterapiaProdutos naturaisElapaconaTrypanosoma cruziChagas diseaseChemotherapyNatural productsElapachone derivativeEffects of a novel β-lapachone derivative on Trypanosoma cruzi: Parasite death involving apoptosis, autophagy and necrosisinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-82991https://www.arca.fiocruz.br/bitstream/icict/18066/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALAnjos, DO Effect of a novel-B.pdfAnjos, DO Effect of a 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dc.title.pt_BR.fl_str_mv Effects of a novel β-lapachone derivative on Trypanosoma cruzi: Parasite death involving apoptosis, autophagy and necrosis
title Effects of a novel β-lapachone derivative on Trypanosoma cruzi: Parasite death involving apoptosis, autophagy and necrosis
spellingShingle Effects of a novel β-lapachone derivative on Trypanosoma cruzi: Parasite death involving apoptosis, autophagy and necrosis
Anjos, Danielle Oliveira dos
Trypanosoma cruzi
Doença de Chagas
Quimioterapia
Produtos naturais
Elapacona
Trypanosoma cruzi
Chagas disease
Chemotherapy
Natural products
Elapachone derivative
title_short Effects of a novel β-lapachone derivative on Trypanosoma cruzi: Parasite death involving apoptosis, autophagy and necrosis
title_full Effects of a novel β-lapachone derivative on Trypanosoma cruzi: Parasite death involving apoptosis, autophagy and necrosis
title_fullStr Effects of a novel β-lapachone derivative on Trypanosoma cruzi: Parasite death involving apoptosis, autophagy and necrosis
title_full_unstemmed Effects of a novel β-lapachone derivative on Trypanosoma cruzi: Parasite death involving apoptosis, autophagy and necrosis
title_sort Effects of a novel β-lapachone derivative on Trypanosoma cruzi: Parasite death involving apoptosis, autophagy and necrosis
author Anjos, Danielle Oliveira dos
author_facet Anjos, Danielle Oliveira dos
Alves, Eliomara Sousa Sobral
Gonçalves, Vinicius Tomaz
Fontes, Sheila Suarez
Nogueira, Mateus Lima
Fontes, Ana Márcia Suarez
Costa, João Batista Neves da
Santos, Fabricio Rios
Santos, Marcos André Vannier dos
author_role author
author2 Alves, Eliomara Sousa Sobral
Gonçalves, Vinicius Tomaz
Fontes, Sheila Suarez
Nogueira, Mateus Lima
Fontes, Ana Márcia Suarez
Costa, João Batista Neves da
Santos, Fabricio Rios
Santos, Marcos André Vannier dos
author2_role author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Anjos, Danielle Oliveira dos
Alves, Eliomara Sousa Sobral
Gonçalves, Vinicius Tomaz
Fontes, Sheila Suarez
Nogueira, Mateus Lima
Fontes, Ana Márcia Suarez
Costa, João Batista Neves da
Santos, Fabricio Rios
Santos, Marcos André Vannier dos
dc.subject.other.pt_BR.fl_str_mv Trypanosoma cruzi
Doença de Chagas
Quimioterapia
Produtos naturais
Elapacona
topic Trypanosoma cruzi
Doença de Chagas
Quimioterapia
Produtos naturais
Elapacona
Trypanosoma cruzi
Chagas disease
Chemotherapy
Natural products
Elapachone derivative
dc.subject.en.pt_BR.fl_str_mv Trypanosoma cruzi
Chagas disease
Chemotherapy
Natural products
Elapachone derivative
description CNPq, PROCAD/Capes PP-SUS, PROEP, INCTINPeTAm, FAPESB, PRONEX/MCT.
publishDate 2016
dc.date.issued.fl_str_mv 2016
dc.date.accessioned.fl_str_mv 2017-03-16T17:40:58Z
dc.date.available.fl_str_mv 2017-03-16T17:40:58Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.citation.fl_str_mv ANJOS, D. O. dos Effects of a novel β-lapachone derivative on Trypanosoma cruzi: Parasite death involving apoptosis, autophagy and necrosis. Drugs and Drug Resistance, v. 6, p. 207e219, 2016.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/18066
dc.identifier.issn.pt_BR.fl_str_mv 0020-7519
dc.identifier.doi.none.fl_str_mv 10.1016/j.ijpddr.2016.10.003
identifier_str_mv ANJOS, D. O. dos Effects of a novel β-lapachone derivative on Trypanosoma cruzi: Parasite death involving apoptosis, autophagy and necrosis. Drugs and Drug Resistance, v. 6, p. 207e219, 2016.
0020-7519
10.1016/j.ijpddr.2016.10.003
url https://www.arca.fiocruz.br/handle/icict/18066
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:Repositório Institucional da FIOCRUZ (ARCA)
instname:Fundação Oswaldo Cruz (FIOCRUZ)
instacron:FIOCRUZ
instname_str Fundação Oswaldo Cruz (FIOCRUZ)
instacron_str FIOCRUZ
institution FIOCRUZ
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