Tamoxifen acts on Trypanosoma cruzi sphingolipid pathway triggering an apoptotic death process

Autores
Landoni, Malena; Piñero, Tamara; Soprano, Luciana L; Garcia-Bournissen, Facundo; Fichera, Laura E.; Esteva, Monica I; Duschak, Vilma G; Couto, Alicia S
Año de publicación
2019
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Fil: Landoni, Malena. Universidad de Buenos Aires, FCEN, Departamento de Química Orgánica - CONICET; Argentina.
Fil: Piñero, Tamara. Universidad de Buenos Aires, FCEN, Departamento de Química Orgánica - CONICET; Argentina.
Fil: Soprano, Luciana L. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Parasitología; Argentina.
Fil: Garcia-Bournissen, Facundo. Instituto Multidisciplinario de Investigaciones en Enfermedades Pedíatricas (IMIPP), CONICET, Hospital de Niños "Ricardo Gutiérrez"; Argentina.
Fil: Fichera, Laura E. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Parasitología; Argentina.
Fil: Esteva, Monica I. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Parasitología; Argentina.
Fil: Duschak, Vilma G. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Parasitología; Argentina.
Fil: Couto, Alicia S. Universidad de Buenos Aires, FCEN, Departamento de Química Orgánica - CONICET; Argentina.
This study shows the effects of tamoxifen, a known estrogen receptor antagonist used in the treatment of breast cancer, on the sphingolipid pathway of Trypanosoma cruzi, searching for potential chemotherapeutic targets. A dose-dependent epimastigote growth inhibition at increasing concentration of tamoxifen was determined. In blood trypomastigotes, treatment with 10 μM showed 90% lysis, while 86% inhibition of intracellular amastigote development was obtained using 50 μM. Lipid extracts from treated and non-treated metabolically labelled epimastigotes evidenced by thin layer chromatography different levels of sphingolipids and MALDI-TOF mass spectrometry analysis assured the identity of the labelled species. Comparison by HPLC-ESI mass spectrometry of lipids, notably exhibited a dramatic increase in the level of ceramide in tamoxifen-treated parasites and a restrained increase of ceramide-1P and sphingosine, indicating that the drug is acting on the enzymes involved in the final breakdown of ceramide. The ultrastructural analysis of treated parasites revealed characteristic morphology of cells undergoing an apoptotic-like death process. Flow cytometry confirmed cell death by an apoptotic-like machinery indicating that tamoxifen triggers this process by acting on the parasitic sphingolipid pathway.
Materia
Lipidómica
Esfingolípidos
Trypanosoma cruzi
Tamoxifeno
Nivel de accesibilidad
acceso abierto
Condiciones de uso
none
Repositorio
Sistema de Gestión del Conocimiento ANLIS MALBRÁN
Institución
Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"
OAI Identificador
oai:sgc.anlis.gob.ar:Publications/123456789/1338
Acceder
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oai_identifier_str oai:sgc.anlis.gob.ar:Publications/123456789/1338
network_acronym_str SGCANLIS
repository_id_str a
network_name_str Sistema de Gestión del Conocimiento ANLIS MALBRÁN
spelling Tamoxifen acts on Trypanosoma cruzi sphingolipid pathway triggering an apoptotic death processLandoni, MalenaPiñero, TamaraSoprano, Luciana LGarcia-Bournissen, FacundoFichera, Laura E.Esteva, Monica IDuschak, Vilma GCouto, Alicia SLipidómicaEsfingolípidosTrypanosoma cruziTamoxifenoFil: Landoni, Malena. Universidad de Buenos Aires, FCEN, Departamento de Química Orgánica - CONICET; Argentina.Fil: Piñero, Tamara. Universidad de Buenos Aires, FCEN, Departamento de Química Orgánica - CONICET; Argentina.Fil: Soprano, Luciana L. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Parasitología; Argentina.Fil: Garcia-Bournissen, Facundo. Instituto Multidisciplinario de Investigaciones en Enfermedades Pedíatricas (IMIPP), CONICET, Hospital de Niños "Ricardo Gutiérrez"; Argentina.Fil: Fichera, Laura E. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Parasitología; Argentina.Fil: Esteva, Monica I. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Parasitología; Argentina.Fil: Duschak, Vilma G. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Parasitología; Argentina.Fil: Couto, Alicia S. Universidad de Buenos Aires, FCEN, Departamento de Química Orgánica - CONICET; Argentina.This study shows the effects of tamoxifen, a known estrogen receptor antagonist used in the treatment of breast cancer, on the sphingolipid pathway of Trypanosoma cruzi, searching for potential chemotherapeutic targets. A dose-dependent epimastigote growth inhibition at increasing concentration of tamoxifen was determined. In blood trypomastigotes, treatment with 10 μM showed 90% lysis, while 86% inhibition of intracellular amastigote development was obtained using 50 μM. Lipid extracts from treated and non-treated metabolically labelled epimastigotes evidenced by thin layer chromatography different levels of sphingolipids and MALDI-TOF mass spectrometry analysis assured the identity of the labelled species. Comparison by HPLC-ESI mass spectrometry of lipids, notably exhibited a dramatic increase in the level of ceramide in tamoxifen-treated parasites and a restrained increase of ceramide-1P and sphingosine, indicating that the drug is acting on the enzymes involved in the final breakdown of ceramide. The ultrastructural analysis of treated parasites revealed characteristic morphology of cells undergoing an apoptotic-like death process. Flow cytometry confirmed cell death by an apoptotic-like machinery indicating that tamoxifen triggers this process by acting on the parasitic sphingolipid pathway.Academic Press2019-08-27info:ar-repo/semantics/articuloinfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdf0006-291Xhttp://sgc.anlis.gob.ar/handle/123456789/133810.1016/j.bbrc.2019.06.149Biochemical and biophysical research communicationsnoneinfo:eu-repo/semantics/openAccessengreponame:Sistema de Gestión del Conocimiento ANLIS MALBRÁNinstname:Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"instacron:ANLIS2025-11-13T10:12:49Zoai:sgc.anlis.gob.ar:Publications/123456789/1338Institucionalhttp://sgc.anlis.gob.ar/Organismo científico-tecnológicoNo correspondehttp://sgc.anlis.gob.ar/oai/biblioteca@anlis.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:a2025-11-13 10:12:50.231Sistema de Gestión del Conocimiento ANLIS MALBRÁN - Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"false
dc.title.none.fl_str_mv Tamoxifen acts on Trypanosoma cruzi sphingolipid pathway triggering an apoptotic death process
title Tamoxifen acts on Trypanosoma cruzi sphingolipid pathway triggering an apoptotic death process
spellingShingle Tamoxifen acts on Trypanosoma cruzi sphingolipid pathway triggering an apoptotic death process
Landoni, Malena
Lipidómica
Esfingolípidos
Trypanosoma cruzi
Tamoxifeno
title_short Tamoxifen acts on Trypanosoma cruzi sphingolipid pathway triggering an apoptotic death process
title_full Tamoxifen acts on Trypanosoma cruzi sphingolipid pathway triggering an apoptotic death process
title_fullStr Tamoxifen acts on Trypanosoma cruzi sphingolipid pathway triggering an apoptotic death process
title_full_unstemmed Tamoxifen acts on Trypanosoma cruzi sphingolipid pathway triggering an apoptotic death process
title_sort Tamoxifen acts on Trypanosoma cruzi sphingolipid pathway triggering an apoptotic death process
dc.creator.none.fl_str_mv Landoni, Malena
Piñero, Tamara
Soprano, Luciana L
Garcia-Bournissen, Facundo
Fichera, Laura E.
Esteva, Monica I
Duschak, Vilma G
Couto, Alicia S
author Landoni, Malena
author_facet Landoni, Malena
Piñero, Tamara
Soprano, Luciana L
Garcia-Bournissen, Facundo
Fichera, Laura E.
Esteva, Monica I
Duschak, Vilma G
Couto, Alicia S
author_role author
author2 Piñero, Tamara
Soprano, Luciana L
Garcia-Bournissen, Facundo
Fichera, Laura E.
Esteva, Monica I
Duschak, Vilma G
Couto, Alicia S
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Lipidómica
Esfingolípidos
Trypanosoma cruzi
Tamoxifeno
topic Lipidómica
Esfingolípidos
Trypanosoma cruzi
Tamoxifeno
dc.description.none.fl_txt_mv Fil: Landoni, Malena. Universidad de Buenos Aires, FCEN, Departamento de Química Orgánica - CONICET; Argentina.
Fil: Piñero, Tamara. Universidad de Buenos Aires, FCEN, Departamento de Química Orgánica - CONICET; Argentina.
Fil: Soprano, Luciana L. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Parasitología; Argentina.
Fil: Garcia-Bournissen, Facundo. Instituto Multidisciplinario de Investigaciones en Enfermedades Pedíatricas (IMIPP), CONICET, Hospital de Niños "Ricardo Gutiérrez"; Argentina.
Fil: Fichera, Laura E. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Parasitología; Argentina.
Fil: Esteva, Monica I. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Parasitología; Argentina.
Fil: Duschak, Vilma G. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Parasitología; Argentina.
Fil: Couto, Alicia S. Universidad de Buenos Aires, FCEN, Departamento de Química Orgánica - CONICET; Argentina.
This study shows the effects of tamoxifen, a known estrogen receptor antagonist used in the treatment of breast cancer, on the sphingolipid pathway of Trypanosoma cruzi, searching for potential chemotherapeutic targets. A dose-dependent epimastigote growth inhibition at increasing concentration of tamoxifen was determined. In blood trypomastigotes, treatment with 10 μM showed 90% lysis, while 86% inhibition of intracellular amastigote development was obtained using 50 μM. Lipid extracts from treated and non-treated metabolically labelled epimastigotes evidenced by thin layer chromatography different levels of sphingolipids and MALDI-TOF mass spectrometry analysis assured the identity of the labelled species. Comparison by HPLC-ESI mass spectrometry of lipids, notably exhibited a dramatic increase in the level of ceramide in tamoxifen-treated parasites and a restrained increase of ceramide-1P and sphingosine, indicating that the drug is acting on the enzymes involved in the final breakdown of ceramide. The ultrastructural analysis of treated parasites revealed characteristic morphology of cells undergoing an apoptotic-like death process. Flow cytometry confirmed cell death by an apoptotic-like machinery indicating that tamoxifen triggers this process by acting on the parasitic sphingolipid pathway.
description Fil: Landoni, Malena. Universidad de Buenos Aires, FCEN, Departamento de Química Orgánica - CONICET; Argentina.
publishDate 2019
dc.date.none.fl_str_mv 2019-08-27
dc.type.none.fl_str_mv info:ar-repo/semantics/articulo
info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv 0006-291X
http://sgc.anlis.gob.ar/handle/123456789/1338
10.1016/j.bbrc.2019.06.149
identifier_str_mv 0006-291X
10.1016/j.bbrc.2019.06.149
url http://sgc.anlis.gob.ar/handle/123456789/1338
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Biochemical and biophysical research communications
dc.rights.none.fl_str_mv none
info:eu-repo/semantics/openAccess
rights_invalid_str_mv none
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Academic Press
publisher.none.fl_str_mv Academic Press
dc.source.none.fl_str_mv reponame:Sistema de Gestión del Conocimiento ANLIS MALBRÁN
instname:Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"
instacron:ANLIS
reponame_str Sistema de Gestión del Conocimiento ANLIS MALBRÁN
collection Sistema de Gestión del Conocimiento ANLIS MALBRÁN
instname_str Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"
instacron_str ANLIS
institution ANLIS
repository.name.fl_str_mv Sistema de Gestión del Conocimiento ANLIS MALBRÁN - Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"
repository.mail.fl_str_mv biblioteca@anlis.gov.ar
_version_ 1848683758154153984
score 12.742515

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