Effects of a novel β-lapachone derivative on Trypanosoma cruzi: Parasite death involving apoptosis, autophagy and necrosis
Autor(a) principal: | |
---|---|
Data de Publicação: | 2016 |
Outros Autores: | , , , , , , , |
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. |
id |
CRUZ_8bda2026edbc4f8c59500900ffbf1f2c |
---|---|
oai_identifier_str |
oai:www.arca.fiocruz.br:icict/18066 |
network_acronym_str |
CRUZ |
network_name_str |
Repositório Institucional da FIOCRUZ (ARCA) |
repository_id_str |
2135 |
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 novel-B.pdfapplication/pdf2604687https://www.arca.fiocruz.br/bitstream/icict/18066/2/Anjos%2c%20DO%20Effect%20of%20a%20novel-B.pdfa792de2bdfe64e9fd85f69eada3276f8MD52TEXTAnjos, DO Effect of a novel-B.pdf.txtAnjos, DO Effect of a novel-B.pdf.txtExtracted texttext/plain74556https://www.arca.fiocruz.br/bitstream/icict/18066/3/Anjos%2c%20DO%20Effect%20of%20a%20novel-B.pdf.txt8945f67f5f858ce5331ce2ad061da5a8MD53icict/180662023-03-15 14:33:28.784oai:www.arca.fiocruz.br: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ório InstitucionalPUBhttps://www.arca.fiocruz.br/oai/requestrepositorio.arca@fiocruz.bropendoar:21352023-03-15T17:33:28Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)false |
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 |
reponame_str |
Repositório Institucional da FIOCRUZ (ARCA) |
collection |
Repositório Institucional da FIOCRUZ (ARCA) |
bitstream.url.fl_str_mv |
https://www.arca.fiocruz.br/bitstream/icict/18066/1/license.txt https://www.arca.fiocruz.br/bitstream/icict/18066/2/Anjos%2c%20DO%20Effect%20of%20a%20novel-B.pdf https://www.arca.fiocruz.br/bitstream/icict/18066/3/Anjos%2c%20DO%20Effect%20of%20a%20novel-B.pdf.txt |
bitstream.checksum.fl_str_mv |
5a560609d32a3863062d77ff32785d58 a792de2bdfe64e9fd85f69eada3276f8 8945f67f5f858ce5331ce2ad061da5a8 |
bitstream.checksumAlgorithm.fl_str_mv |
MD5 MD5 MD5 |
repository.name.fl_str_mv |
Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ) |
repository.mail.fl_str_mv |
repositorio.arca@fiocruz.br |
_version_ |
1813009057543356416 |