P53 tumor suppressor is required for efficient execution of the death program following treatment with a cytotoxic limonoid obtained from Melia azedarach

Autores
Joray, Mariana Belén; Villafañez, Florencia; González, María Laura; Crespo, Maria Ines; Laiolo, Jerónimo; Palacios, Sara Maria; Bocco, Jose Luis; Soria, Ramiro Gaston; Carpinella, Maria Cecilia
Año de publicación
2017
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
This work examines the antitumor activity of an isomeric mixture (1), composed of the limonoids meliartenin and its interchangeable isomer 12-hydroxyamoorastatin. The results obtained showed that 1 displayed outstanding cytotoxic activity against CCRF-CEM, K562, A549 and HCT116 cells, with a highly selective effect on the latter, with an IC50 value of 0.2 μM. Based on this finding, HCT116 cells were selected to study the mechanism of action of 1. Cell cycle analysis revealed that 1 induced sustained arrest in the S-phase, which was followed by the triggering of apoptotic cell death and reduced clonogenic capacity. This cytotoxicity was seen to be preceded by the upregulation of the tumor suppressor p53 and its target effector p21. In addition, it was found that p53 expression was required for efficient cell death induction, and thus that the toxicity of 1 relies mainly on p53-dependent mechanisms. Taken together, these findings position 1 as a potent antitumor agent, with potential for the development of novel chemotherapeutic drugs based on the induction of S-phase arrest.
Fil: Joray, Mariana Belén. Universidad Católica de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Villafañez, Florencia. Universidad Nacional de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: González, María Laura. Universidad Católica de Córdoba; Argentina
Fil: Crespo, Maria Ines. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Católica de Córdoba; Argentina
Fil: Laiolo, Jerónimo. Universidad Católica de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Palacios, Sara Maria. Universidad Católica de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Bocco, Jose Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Soria, Ramiro Gaston. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Carpinella, Maria Cecilia. Universidad Católica de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Materia
Meliartenin12
Hydroxyamoorastatin
Cytotoxicity
Apoptosis
Cell Cycle Arrest
Hct116
P53
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/47796
Acceder
id CONICETDig_ba576cdf252dbb41dbd1b21a9aea7f79
oai_identifier_str oai:ri.conicet.gov.ar:11336/47796
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling P53 tumor suppressor is required for efficient execution of the death program following treatment with a cytotoxic limonoid obtained from Melia azedarachJoray, Mariana BelénVillafañez, FlorenciaGonzález, María LauraCrespo, Maria InesLaiolo, JerónimoPalacios, Sara MariaBocco, Jose LuisSoria, Ramiro GastonCarpinella, Maria CeciliaMeliartenin12HydroxyamoorastatinCytotoxicityApoptosisCell Cycle ArrestHct116P53https://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3This work examines the antitumor activity of an isomeric mixture (1), composed of the limonoids meliartenin and its interchangeable isomer 12-hydroxyamoorastatin. The results obtained showed that 1 displayed outstanding cytotoxic activity against CCRF-CEM, K562, A549 and HCT116 cells, with a highly selective effect on the latter, with an IC50 value of 0.2 μM. Based on this finding, HCT116 cells were selected to study the mechanism of action of 1. Cell cycle analysis revealed that 1 induced sustained arrest in the S-phase, which was followed by the triggering of apoptotic cell death and reduced clonogenic capacity. This cytotoxicity was seen to be preceded by the upregulation of the tumor suppressor p53 and its target effector p21. In addition, it was found that p53 expression was required for efficient cell death induction, and thus that the toxicity of 1 relies mainly on p53-dependent mechanisms. Taken together, these findings position 1 as a potent antitumor agent, with potential for the development of novel chemotherapeutic drugs based on the induction of S-phase arrest.Fil: Joray, Mariana Belén. Universidad Católica de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Villafañez, Florencia. Universidad Nacional de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: González, María Laura. Universidad Católica de Córdoba; ArgentinaFil: Crespo, Maria Ines. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Católica de Córdoba; ArgentinaFil: Laiolo, Jerónimo. Universidad Católica de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Palacios, Sara Maria. Universidad Católica de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Bocco, Jose Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Soria, Ramiro Gaston. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Carpinella, Maria Cecilia. Universidad Católica de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaPergamon-Elsevier Science Ltd2017-11-29info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/47796Joray, Mariana Belén; Villafañez, Florencia; González, María Laura; Crespo, Maria Ines; Laiolo, Jerónimo; et al.; P53 tumor suppressor is required for efficient execution of the death program following treatment with a cytotoxic limonoid obtained from Melia azedarach; Pergamon-Elsevier Science Ltd; Food And Chemical Toxicology; 109; Part 2; 29-11-2017; 888-8970278-6915CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S027869151730217Xinfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.fct.2017.04.039info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2026-06-10T09:56:44Zoai:ri.conicet.gov.ar:11336/47796instacron: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:34982026-06-10 09:56:44.728CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv P53 tumor suppressor is required for efficient execution of the death program following treatment with a cytotoxic limonoid obtained from Melia azedarach
title P53 tumor suppressor is required for efficient execution of the death program following treatment with a cytotoxic limonoid obtained from Melia azedarach
spellingShingle P53 tumor suppressor is required for efficient execution of the death program following treatment with a cytotoxic limonoid obtained from Melia azedarach
Joray, Mariana Belén
Meliartenin12
Hydroxyamoorastatin
Cytotoxicity
Apoptosis
Cell Cycle Arrest
Hct116
P53
title_short P53 tumor suppressor is required for efficient execution of the death program following treatment with a cytotoxic limonoid obtained from Melia azedarach
title_full P53 tumor suppressor is required for efficient execution of the death program following treatment with a cytotoxic limonoid obtained from Melia azedarach
title_fullStr P53 tumor suppressor is required for efficient execution of the death program following treatment with a cytotoxic limonoid obtained from Melia azedarach
title_full_unstemmed P53 tumor suppressor is required for efficient execution of the death program following treatment with a cytotoxic limonoid obtained from Melia azedarach
title_sort P53 tumor suppressor is required for efficient execution of the death program following treatment with a cytotoxic limonoid obtained from Melia azedarach
dc.creator.none.fl_str_mv Joray, Mariana Belén
Villafañez, Florencia
González, María Laura
Crespo, Maria Ines
Laiolo, Jerónimo
Palacios, Sara Maria
Bocco, Jose Luis
Soria, Ramiro Gaston
Carpinella, Maria Cecilia
author Joray, Mariana Belén
author_facet Joray, Mariana Belén
Villafañez, Florencia
González, María Laura
Crespo, Maria Ines
Laiolo, Jerónimo
Palacios, Sara Maria
Bocco, Jose Luis
Soria, Ramiro Gaston
Carpinella, Maria Cecilia
author_role author
author2 Villafañez, Florencia
González, María Laura
Crespo, Maria Ines
Laiolo, Jerónimo
Palacios, Sara Maria
Bocco, Jose Luis
Soria, Ramiro Gaston
Carpinella, Maria Cecilia
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Meliartenin12
Hydroxyamoorastatin
Cytotoxicity
Apoptosis
Cell Cycle Arrest
Hct116
P53
topic Meliartenin12
Hydroxyamoorastatin
Cytotoxicity
Apoptosis
Cell Cycle Arrest
Hct116
P53
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv This work examines the antitumor activity of an isomeric mixture (1), composed of the limonoids meliartenin and its interchangeable isomer 12-hydroxyamoorastatin. The results obtained showed that 1 displayed outstanding cytotoxic activity against CCRF-CEM, K562, A549 and HCT116 cells, with a highly selective effect on the latter, with an IC50 value of 0.2 μM. Based on this finding, HCT116 cells were selected to study the mechanism of action of 1. Cell cycle analysis revealed that 1 induced sustained arrest in the S-phase, which was followed by the triggering of apoptotic cell death and reduced clonogenic capacity. This cytotoxicity was seen to be preceded by the upregulation of the tumor suppressor p53 and its target effector p21. In addition, it was found that p53 expression was required for efficient cell death induction, and thus that the toxicity of 1 relies mainly on p53-dependent mechanisms. Taken together, these findings position 1 as a potent antitumor agent, with potential for the development of novel chemotherapeutic drugs based on the induction of S-phase arrest.
Fil: Joray, Mariana Belén. Universidad Católica de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Villafañez, Florencia. Universidad Nacional de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: González, María Laura. Universidad Católica de Córdoba; Argentina
Fil: Crespo, Maria Ines. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Católica de Córdoba; Argentina
Fil: Laiolo, Jerónimo. Universidad Católica de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Palacios, Sara Maria. Universidad Católica de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Bocco, Jose Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Soria, Ramiro Gaston. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Carpinella, Maria Cecilia. Universidad Católica de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
description This work examines the antitumor activity of an isomeric mixture (1), composed of the limonoids meliartenin and its interchangeable isomer 12-hydroxyamoorastatin. The results obtained showed that 1 displayed outstanding cytotoxic activity against CCRF-CEM, K562, A549 and HCT116 cells, with a highly selective effect on the latter, with an IC50 value of 0.2 μM. Based on this finding, HCT116 cells were selected to study the mechanism of action of 1. Cell cycle analysis revealed that 1 induced sustained arrest in the S-phase, which was followed by the triggering of apoptotic cell death and reduced clonogenic capacity. This cytotoxicity was seen to be preceded by the upregulation of the tumor suppressor p53 and its target effector p21. In addition, it was found that p53 expression was required for efficient cell death induction, and thus that the toxicity of 1 relies mainly on p53-dependent mechanisms. Taken together, these findings position 1 as a potent antitumor agent, with potential for the development of novel chemotherapeutic drugs based on the induction of S-phase arrest.
publishDate 2017
dc.date.none.fl_str_mv 2017-11-29
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/11336/47796
Joray, Mariana Belén; Villafañez, Florencia; González, María Laura; Crespo, Maria Ines; Laiolo, Jerónimo; et al.; P53 tumor suppressor is required for efficient execution of the death program following treatment with a cytotoxic limonoid obtained from Melia azedarach; Pergamon-Elsevier Science Ltd; Food And Chemical Toxicology; 109; Part 2; 29-11-2017; 888-897
0278-6915
CONICET Digital
CONICET
url http://hdl.handle.net/11336/47796
identifier_str_mv Joray, Mariana Belén; Villafañez, Florencia; González, María Laura; Crespo, Maria Ines; Laiolo, Jerónimo; et al.; P53 tumor suppressor is required for efficient execution of the death program following treatment with a cytotoxic limonoid obtained from Melia azedarach; Pergamon-Elsevier Science Ltd; Food And Chemical Toxicology; 109; Part 2; 29-11-2017; 888-897
0278-6915
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/pii/S027869151730217X
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.fct.2017.04.039
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
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 12.997949

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