15-Deoxi-Δ12,14-prostaglandin J2 is a tubulin-binding agent that destabilizes microtubules and induces mitotic arrest

Autores
Cocca, Claudia Marcela; Dorado, Jorge; Calvo, Enrique; López, Juan Antonio; Santos, Angel; Perez Castillo, Ana
Año de publicación
2009
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
15-Deoxi-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)) is known to play an important role in the pathophysiology of carcinogenesis, however, the molecular mechanisms underlying these effects are not yet fully understood. Recently, we have shown that 15d-PGJ(2) is a potent inducer of breast cancer cell death and that this effect is associated with a disruption of the microtubule cytoskeletal network. Here, we show that treatment of the MCF-7 breast cancer cell line with 15d-PGJ(2) induces an accumulation of cells in the G(2)/M compartment of the cell cycle and a marked disruption of the microtubule network. 15d-PGJ(2) treatment causes mitotic abnormalities that consist of failure to form a stable metaphase plate, incapacity to progress through anaphase, and failure to complete cytokinesis. 15d-PGJ(2) binds to tubulin through the formation of a covalent adduct with at least four cysteine residues in alpha- and beta-tubulin, as detected by hybrid triple-quadrupole mass spectrometry analysis. Overall, these results support the hypothesis that microtubule disruption and mitotic arrest, as a consequence of the binding of 15d-PGJ(2) to tubulin, can represent one important pathway leading to breast cancer cell death.
Fil: Cocca, Claudia Marcela. Universidad Autónoma de Madrid; España. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
Fil: Dorado, Jorge. Universidad Autónoma de Madrid; España
Fil: Calvo, Enrique. Centro Nacional de Investigaciones Cardiovasculares; España
Fil: López, Juan Antonio. Centro Nacional de Investigaciones Cardiovasculares; España
Fil: Santos, Angel. Universidad Complutense de Madrid; España
Fil: Perez Castillo, Ana. Universidad Autónoma de Madrid; España
Materia
15D-PGJ2
CANCER
CELL DEATH
CYTOSKELETON
MITOSIS
TUBULIN
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/137309
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/137309
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling 15-Deoxi-Δ12,14-prostaglandin J2 is a tubulin-binding agent that destabilizes microtubules and induces mitotic arrestCocca, Claudia MarcelaDorado, JorgeCalvo, EnriqueLópez, Juan AntonioSantos, AngelPerez Castillo, Ana15D-PGJ2CANCERCELL DEATHCYTOSKELETONMITOSISTUBULINhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/115-Deoxi-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)) is known to play an important role in the pathophysiology of carcinogenesis, however, the molecular mechanisms underlying these effects are not yet fully understood. Recently, we have shown that 15d-PGJ(2) is a potent inducer of breast cancer cell death and that this effect is associated with a disruption of the microtubule cytoskeletal network. Here, we show that treatment of the MCF-7 breast cancer cell line with 15d-PGJ(2) induces an accumulation of cells in the G(2)/M compartment of the cell cycle and a marked disruption of the microtubule network. 15d-PGJ(2) treatment causes mitotic abnormalities that consist of failure to form a stable metaphase plate, incapacity to progress through anaphase, and failure to complete cytokinesis. 15d-PGJ(2) binds to tubulin through the formation of a covalent adduct with at least four cysteine residues in alpha- and beta-tubulin, as detected by hybrid triple-quadrupole mass spectrometry analysis. Overall, these results support the hypothesis that microtubule disruption and mitotic arrest, as a consequence of the binding of 15d-PGJ(2) to tubulin, can represent one important pathway leading to breast cancer cell death.Fil: Cocca, Claudia Marcela. Universidad Autónoma de Madrid; España. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Dorado, Jorge. Universidad Autónoma de Madrid; EspañaFil: Calvo, Enrique. Centro Nacional de Investigaciones Cardiovasculares; EspañaFil: López, Juan Antonio. Centro Nacional de Investigaciones Cardiovasculares; EspañaFil: Santos, Angel. Universidad Complutense de Madrid; EspañaFil: Perez Castillo, Ana. Universidad Autónoma de Madrid; EspañaPergamon-Elsevier Science Ltd2009-11info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/137309Cocca, Claudia Marcela; Dorado, Jorge; Calvo, Enrique; López, Juan Antonio; Santos, Angel; et al.; 15-Deoxi-Δ12,14-prostaglandin J2 is a tubulin-binding agent that destabilizes microtubules and induces mitotic arrest; Pergamon-Elsevier Science Ltd; Biochemical Pharmacology; 78; 10; 11-2009; 1330-13390006-2952CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/abs/pii/S0006295209005929info:eu-repo/semantics/altIdentifier/doi/10.1016/j.bcp.2009.06.100info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-11-26T08:37:22Zoai:ri.conicet.gov.ar:11336/137309instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-11-26 08:37:22.737CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv 15-Deoxi-Δ12,14-prostaglandin J2 is a tubulin-binding agent that destabilizes microtubules and induces mitotic arrest
title 15-Deoxi-Δ12,14-prostaglandin J2 is a tubulin-binding agent that destabilizes microtubules and induces mitotic arrest
spellingShingle 15-Deoxi-Δ12,14-prostaglandin J2 is a tubulin-binding agent that destabilizes microtubules and induces mitotic arrest
Cocca, Claudia Marcela
15D-PGJ2
CANCER
CELL DEATH
CYTOSKELETON
MITOSIS
TUBULIN
title_short 15-Deoxi-Δ12,14-prostaglandin J2 is a tubulin-binding agent that destabilizes microtubules and induces mitotic arrest
title_full 15-Deoxi-Δ12,14-prostaglandin J2 is a tubulin-binding agent that destabilizes microtubules and induces mitotic arrest
title_fullStr 15-Deoxi-Δ12,14-prostaglandin J2 is a tubulin-binding agent that destabilizes microtubules and induces mitotic arrest
title_full_unstemmed 15-Deoxi-Δ12,14-prostaglandin J2 is a tubulin-binding agent that destabilizes microtubules and induces mitotic arrest
title_sort 15-Deoxi-Δ12,14-prostaglandin J2 is a tubulin-binding agent that destabilizes microtubules and induces mitotic arrest
dc.creator.none.fl_str_mv Cocca, Claudia Marcela
Dorado, Jorge
Calvo, Enrique
López, Juan Antonio
Santos, Angel
Perez Castillo, Ana
author Cocca, Claudia Marcela
author_facet Cocca, Claudia Marcela
Dorado, Jorge
Calvo, Enrique
López, Juan Antonio
Santos, Angel
Perez Castillo, Ana
author_role author
author2 Dorado, Jorge
Calvo, Enrique
López, Juan Antonio
Santos, Angel
Perez Castillo, Ana
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv 15D-PGJ2
CANCER
CELL DEATH
CYTOSKELETON
MITOSIS
TUBULIN
topic 15D-PGJ2
CANCER
CELL DEATH
CYTOSKELETON
MITOSIS
TUBULIN
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv 15-Deoxi-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)) is known to play an important role in the pathophysiology of carcinogenesis, however, the molecular mechanisms underlying these effects are not yet fully understood. Recently, we have shown that 15d-PGJ(2) is a potent inducer of breast cancer cell death and that this effect is associated with a disruption of the microtubule cytoskeletal network. Here, we show that treatment of the MCF-7 breast cancer cell line with 15d-PGJ(2) induces an accumulation of cells in the G(2)/M compartment of the cell cycle and a marked disruption of the microtubule network. 15d-PGJ(2) treatment causes mitotic abnormalities that consist of failure to form a stable metaphase plate, incapacity to progress through anaphase, and failure to complete cytokinesis. 15d-PGJ(2) binds to tubulin through the formation of a covalent adduct with at least four cysteine residues in alpha- and beta-tubulin, as detected by hybrid triple-quadrupole mass spectrometry analysis. Overall, these results support the hypothesis that microtubule disruption and mitotic arrest, as a consequence of the binding of 15d-PGJ(2) to tubulin, can represent one important pathway leading to breast cancer cell death.
Fil: Cocca, Claudia Marcela. Universidad Autónoma de Madrid; España. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
Fil: Dorado, Jorge. Universidad Autónoma de Madrid; España
Fil: Calvo, Enrique. Centro Nacional de Investigaciones Cardiovasculares; España
Fil: López, Juan Antonio. Centro Nacional de Investigaciones Cardiovasculares; España
Fil: Santos, Angel. Universidad Complutense de Madrid; España
Fil: Perez Castillo, Ana. Universidad Autónoma de Madrid; España
description 15-Deoxi-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)) is known to play an important role in the pathophysiology of carcinogenesis, however, the molecular mechanisms underlying these effects are not yet fully understood. Recently, we have shown that 15d-PGJ(2) is a potent inducer of breast cancer cell death and that this effect is associated with a disruption of the microtubule cytoskeletal network. Here, we show that treatment of the MCF-7 breast cancer cell line with 15d-PGJ(2) induces an accumulation of cells in the G(2)/M compartment of the cell cycle and a marked disruption of the microtubule network. 15d-PGJ(2) treatment causes mitotic abnormalities that consist of failure to form a stable metaphase plate, incapacity to progress through anaphase, and failure to complete cytokinesis. 15d-PGJ(2) binds to tubulin through the formation of a covalent adduct with at least four cysteine residues in alpha- and beta-tubulin, as detected by hybrid triple-quadrupole mass spectrometry analysis. Overall, these results support the hypothesis that microtubule disruption and mitotic arrest, as a consequence of the binding of 15d-PGJ(2) to tubulin, can represent one important pathway leading to breast cancer cell death.
publishDate 2009
dc.date.none.fl_str_mv 2009-11
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/137309
Cocca, Claudia Marcela; Dorado, Jorge; Calvo, Enrique; López, Juan Antonio; Santos, Angel; et al.; 15-Deoxi-Δ12,14-prostaglandin J2 is a tubulin-binding agent that destabilizes microtubules and induces mitotic arrest; Pergamon-Elsevier Science Ltd; Biochemical Pharmacology; 78; 10; 11-2009; 1330-1339
0006-2952
CONICET Digital
CONICET
url http://hdl.handle.net/11336/137309
identifier_str_mv Cocca, Claudia Marcela; Dorado, Jorge; Calvo, Enrique; López, Juan Antonio; Santos, Angel; et al.; 15-Deoxi-Δ12,14-prostaglandin J2 is a tubulin-binding agent that destabilizes microtubules and induces mitotic arrest; Pergamon-Elsevier Science Ltd; Biochemical Pharmacology; 78; 10; 11-2009; 1330-1339
0006-2952
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/abs/pii/S0006295209005929
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.bcp.2009.06.100
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Pergamon-Elsevier Science Ltd
publisher.none.fl_str_mv Pergamon-Elsevier Science Ltd
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.011256

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