New findings in the signaling pathways of cis and trans platinum Iodido complexes' interaction with DNA of cancer cells

We have selected a series of aliphatic amine platinum compounds bearing chloride and/or iodide as the leaving groups. The complexes' cytotoxicity and interaction with DNA indicated differences in the reactivity. Now, we are reporting on the analysis of their molecular mechanism of action on gas...

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Autores: Gómez Quiroga, Adoración, Cama, Marta, Pajuelo-Lozano, Natalia, Álvarez Valdés, Amparo, Sánchez Pérez, María Isabel
Tipo de recurso: artículo
Fecha de publicación:2019
País:España
Institución:Universidad Autónoma de Madrid
Repositorio:Biblos-e Archivo. Repositorio Institucional de la UAM
Idioma:inglés
OAI Identifier:oai:repositorio.uam.es:10486/713787
Acceso en línea:http://hdl.handle.net/10486/713787
https://dx.doi.org/10.1021/acsomega.9b02831
Access Level:acceso abierto
Palabra clave:Cisplatin
anticarcinogen
drug screening
Medicina
Química
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spelling New findings in the signaling pathways of cis and trans platinum Iodido complexes' interaction with DNA of cancer cellsGómez Quiroga, AdoraciónCama, MartaPajuelo-Lozano, NataliaÁlvarez Valdés, AmparoSánchez Pérez, María IsabelCisplatinanticarcinogendrug screeningMedicinaQuímicaWe have selected a series of aliphatic amine platinum compounds bearing chloride and/or iodide as the leaving groups. The complexes' cytotoxicity and interaction with DNA indicated differences in the reactivity. Now, we are reporting on the analysis of their molecular mechanism of action on gastric cancer cells. Our data reveals differences between them. Chlorido drugs showed similar behavior to cisplatin; they both required p53 to induce apoptosis but only cis-ipa showed DNA damage requirement for apoptosis induction. On the contrary, cis and trans iodido induced cell death independent of p53 activity, and they induced cell death through Bid activation, so their toxicity could be enhanced in a combined treatment with novel Bcl-2 protein family inhibitors. We also report the structural features of the DNA adduct for one of the complexes by X-ray diffraction. These findings represent a step forward in the search for new platinum-derived agents more specific and effective in the treatment of cancerAuthors A.G.Q., M.C., and A.A.-V. received funding from MINECO CTQ2015-68779-R. I.S.P. received funding from P17-01401 (supported by FEDER funds) from Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos III, SpainNPL is a fellow of the Programa de Doctorado Biociencias Moleculares UAM, Madrid, Spain. NPL was supported by a fellowship Programa de Formación de Profesorado Universitario REF: FPU15/04669American Chemical SocietyDepartamento de BioquímicaDepartamento de Química InorgánicaFacultad de CienciasFacultad de Medicina20192019-12-03research articlehttp://purl.org/coar/resource_type/c_2df8fbb1VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10486/713787https://dx.doi.org/10.1021/acsomega.9b02831reponame:Biblos-e Archivo. Repositorio Institucional de la UAMinstname:Universidad Autónoma de MadridInglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:repositorio.uam.es:10486/7137872026-06-23T12:46:27Z
dc.title.none.fl_str_mv New findings in the signaling pathways of cis and trans platinum Iodido complexes' interaction with DNA of cancer cells
title New findings in the signaling pathways of cis and trans platinum Iodido complexes' interaction with DNA of cancer cells
spellingShingle New findings in the signaling pathways of cis and trans platinum Iodido complexes' interaction with DNA of cancer cells
Gómez Quiroga, Adoración
Cisplatin
anticarcinogen
drug screening
Medicina
Química
title_short New findings in the signaling pathways of cis and trans platinum Iodido complexes' interaction with DNA of cancer cells
title_full New findings in the signaling pathways of cis and trans platinum Iodido complexes' interaction with DNA of cancer cells
title_fullStr New findings in the signaling pathways of cis and trans platinum Iodido complexes' interaction with DNA of cancer cells
title_full_unstemmed New findings in the signaling pathways of cis and trans platinum Iodido complexes' interaction with DNA of cancer cells
title_sort New findings in the signaling pathways of cis and trans platinum Iodido complexes' interaction with DNA of cancer cells
dc.creator.none.fl_str_mv Gómez Quiroga, Adoración
Cama, Marta
Pajuelo-Lozano, Natalia
Álvarez Valdés, Amparo
Sánchez Pérez, María Isabel
author Gómez Quiroga, Adoración
author_facet Gómez Quiroga, Adoración
Cama, Marta
Pajuelo-Lozano, Natalia
Álvarez Valdés, Amparo
Sánchez Pérez, María Isabel
author_role author
author2 Cama, Marta
Pajuelo-Lozano, Natalia
Álvarez Valdés, Amparo
Sánchez Pérez, María Isabel
author2_role author
author
author
author
dc.contributor.none.fl_str_mv Departamento de Bioquímica
Departamento de Química Inorgánica
Facultad de Ciencias
Facultad de Medicina
dc.subject.none.fl_str_mv Cisplatin
anticarcinogen
drug screening
Medicina
Química
topic Cisplatin
anticarcinogen
drug screening
Medicina
Química
description We have selected a series of aliphatic amine platinum compounds bearing chloride and/or iodide as the leaving groups. The complexes' cytotoxicity and interaction with DNA indicated differences in the reactivity. Now, we are reporting on the analysis of their molecular mechanism of action on gastric cancer cells. Our data reveals differences between them. Chlorido drugs showed similar behavior to cisplatin; they both required p53 to induce apoptosis but only cis-ipa showed DNA damage requirement for apoptosis induction. On the contrary, cis and trans iodido induced cell death independent of p53 activity, and they induced cell death through Bid activation, so their toxicity could be enhanced in a combined treatment with novel Bcl-2 protein family inhibitors. We also report the structural features of the DNA adduct for one of the complexes by X-ray diffraction. These findings represent a step forward in the search for new platinum-derived agents more specific and effective in the treatment of cancer
publishDate 2019
dc.date.none.fl_str_mv 2019
2019-12-03
dc.type.none.fl_str_mv research article
http://purl.org/coar/resource_type/c_2df8fbb1
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10486/713787
https://dx.doi.org/10.1021/acsomega.9b02831
url http://hdl.handle.net/10486/713787
https://dx.doi.org/10.1021/acsomega.9b02831
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv American Chemical Society
publisher.none.fl_str_mv American Chemical Society
dc.source.none.fl_str_mv reponame:Biblos-e Archivo. Repositorio Institucional de la UAM
instname:Universidad Autónoma de Madrid
instname_str Universidad Autónoma de Madrid
reponame_str Biblos-e Archivo. Repositorio Institucional de la UAM
collection Biblos-e Archivo. Repositorio Institucional de la UAM
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