Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/18066
Title: Effects of a novel β-lapachone derivative on Trypanosoma cruzi: Parasite death involving apoptosis, autophagy and necrosis
Authors: 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
Affilliation: 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, Brasil
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Biologia Parasitária. Salvador, BA, Brasil
Universidade Federal Rural do Rio de Janeiro. UFRRJ. Instituto de Química. Rio de Janeiro, RJ, Brasil
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Biologia Parasitária. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Biologia Parasitária. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Biologia Parasitária. Salvador, BA, Brasil
Universidade Federal Rural do Rio de Janeiro. UFRRJ. Instituto de Química. Rio de Janeiro, RJ, Brasil
Universidade Federal de Mato Grosso. UFMT. Faculdade de Medicina. Cuiabá, MG, Brasil
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Biologia Parasitária. Salvador, BA, Brasil
Abstract: Natural 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.
Keywords: Trypanosoma cruzi
Chagas disease
Chemotherapy
Natural products
Elapachone derivative
keywords: Trypanosoma cruzi
Doença de Chagas
Quimioterapia
Produtos naturais
Elapacona
Issue Date: 2016
Publisher: Elsevier
Citation: 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.
DOI: 10.1016/j.ijpddr.2016.10.003
ISSN: 0020-7519
Copyright: open access
Appears in Collections:BA - IGM - Artigos de Periódicos

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