Gold(III) bis(thiosemicarbazonate) compounds in breast cancer cells: Cytotoxicity and thioredoxin reductase targeting

Gold(III) compounds have received increasing attention in cancer research. Three gold complexes of general formula [AuIIIL]Cl, where L is benzil bis(thiosemicarbazonate), compound 1, benzil bis(4-methyl-3-thiosemicarbazonate), compound 2, or benzil bis(4-cyclohexyl-3-thiosemicarbazonate), compound 3...

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Detalles Bibliográficos
Autores: Rodríguez Fanjul, Vanessa, López Torres, Elena Sofía, Mendiola Martín, María Antonia, Pizarro, Ana María
Tipo de recurso: artículo
Fecha de publicación:2018
País:España
Institución:Universidad Autónoma de Madrid
Repositorio:Biblos-e Archivo. Repositorio Institucional de la UAM
Idioma:inglés
OAI Identifier:oai:repositorio.uam.es:10486/709618
Acceso en línea:http://hdl.handle.net/10486/709618
https://dx.doi.org/10.1016/j.ejmech.2018.02.009
Access Level:acceso abierto
Palabra clave:Cisplatin
Gold(III)
Thiosemicarbazones
Reactive Oxygen Species
Thioredoxin Reductase
Química
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spelling Gold(III) bis(thiosemicarbazonate) compounds in breast cancer cells: Cytotoxicity and thioredoxin reductase targetingRodríguez Fanjul, VanessaLópez Torres, Elena SofíaMendiola Martín, María AntoniaPizarro, Ana MaríaCisplatinGold(III)ThiosemicarbazonesReactive Oxygen SpeciesThioredoxin ReductaseQuímicaGold(III) compounds have received increasing attention in cancer research. Three gold complexes of general formula [AuIIIL]Cl, where L is benzil bis(thiosemicarbazonate), compound 1, benzil bis(4-methyl-3-thiosemicarbazonate), compound 2, or benzil bis(4-cyclohexyl-3-thiosemicarbazonate), compound 3, have been synthesized and fully characterized, including the X-ray crystal structure of compound 3, confirming square-planar geometry around the gold(III) centre. Compound 1 showed moderate cytotoxicity and accumulation in MCF7 breast cancer cells but did not inhibit thioredoxin reductase (TrxR) activity and did not induce reactive oxygen species (ROS) production. Compound 2, the least cytotoxic, was found to be capable of modestly inhibiting TrxR activity and produced low levels of ROS in the MCF7 cell line. The most cytotoxic compound, 3, had the highest cellular accumulation and its distribution pattern showed a clear preference for the cytosol and mitochondria of MCF7 cells. It readily hampered intracellular TrxR activity leading to a dramatic alteration of the cellular redox state and to the induction of cell deathThis research was supported by the EC (FP7-PEOPLE-2013-CIG, no. 631396), the MINECO of Spain (RYC-2012-11231, and CTQ2014-60100-R), the Instituto de Salud Carlos III (PS09/00963), and the Comunidad Autonoma de Madrid (S2013/MIT-2850)ElsevierDepartamento de Química InorgánicaFacultad de Ciencias20182018-03-25research articlehttp://purl.org/coar/resource_type/c_2df8fbb1AMhttp://purl.org/coar/version/c_ab4af688f83e57aainfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10486/709618https://dx.doi.org/10.1016/j.ejmech.2018.02.009reponame:Biblos-e Archivo. Repositorio Institucional de la UAMinstname:Universidad Autónoma de MadridInglésengEuropean Commission http://dx.doi.org/10.13039/501100000780 Framework Programme Seven 631396open accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:repositorio.uam.es:10486/7096182026-06-23T12:46:27Z
dc.title.none.fl_str_mv Gold(III) bis(thiosemicarbazonate) compounds in breast cancer cells: Cytotoxicity and thioredoxin reductase targeting
title Gold(III) bis(thiosemicarbazonate) compounds in breast cancer cells: Cytotoxicity and thioredoxin reductase targeting
spellingShingle Gold(III) bis(thiosemicarbazonate) compounds in breast cancer cells: Cytotoxicity and thioredoxin reductase targeting
Rodríguez Fanjul, Vanessa
Cisplatin
Gold(III)
Thiosemicarbazones
Reactive Oxygen Species
Thioredoxin Reductase
Química
title_short Gold(III) bis(thiosemicarbazonate) compounds in breast cancer cells: Cytotoxicity and thioredoxin reductase targeting
title_full Gold(III) bis(thiosemicarbazonate) compounds in breast cancer cells: Cytotoxicity and thioredoxin reductase targeting
title_fullStr Gold(III) bis(thiosemicarbazonate) compounds in breast cancer cells: Cytotoxicity and thioredoxin reductase targeting
title_full_unstemmed Gold(III) bis(thiosemicarbazonate) compounds in breast cancer cells: Cytotoxicity and thioredoxin reductase targeting
title_sort Gold(III) bis(thiosemicarbazonate) compounds in breast cancer cells: Cytotoxicity and thioredoxin reductase targeting
dc.creator.none.fl_str_mv Rodríguez Fanjul, Vanessa
López Torres, Elena Sofía
Mendiola Martín, María Antonia
Pizarro, Ana María
author Rodríguez Fanjul, Vanessa
author_facet Rodríguez Fanjul, Vanessa
López Torres, Elena Sofía
Mendiola Martín, María Antonia
Pizarro, Ana María
author_role author
author2 López Torres, Elena Sofía
Mendiola Martín, María Antonia
Pizarro, Ana María
author2_role author
author
author
dc.contributor.none.fl_str_mv Departamento de Química Inorgánica
Facultad de Ciencias
dc.subject.none.fl_str_mv Cisplatin
Gold(III)
Thiosemicarbazones
Reactive Oxygen Species
Thioredoxin Reductase
Química
topic Cisplatin
Gold(III)
Thiosemicarbazones
Reactive Oxygen Species
Thioredoxin Reductase
Química
description Gold(III) compounds have received increasing attention in cancer research. Three gold complexes of general formula [AuIIIL]Cl, where L is benzil bis(thiosemicarbazonate), compound 1, benzil bis(4-methyl-3-thiosemicarbazonate), compound 2, or benzil bis(4-cyclohexyl-3-thiosemicarbazonate), compound 3, have been synthesized and fully characterized, including the X-ray crystal structure of compound 3, confirming square-planar geometry around the gold(III) centre. Compound 1 showed moderate cytotoxicity and accumulation in MCF7 breast cancer cells but did not inhibit thioredoxin reductase (TrxR) activity and did not induce reactive oxygen species (ROS) production. Compound 2, the least cytotoxic, was found to be capable of modestly inhibiting TrxR activity and produced low levels of ROS in the MCF7 cell line. The most cytotoxic compound, 3, had the highest cellular accumulation and its distribution pattern showed a clear preference for the cytosol and mitochondria of MCF7 cells. It readily hampered intracellular TrxR activity leading to a dramatic alteration of the cellular redox state and to the induction of cell death
publishDate 2018
dc.date.none.fl_str_mv 2018
2018-03-25
dc.type.none.fl_str_mv research article
http://purl.org/coar/resource_type/c_2df8fbb1
AM
http://purl.org/coar/version/c_ab4af688f83e57aa
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10486/709618
https://dx.doi.org/10.1016/j.ejmech.2018.02.009
url http://hdl.handle.net/10486/709618
https://dx.doi.org/10.1016/j.ejmech.2018.02.009
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv European Commission http://dx.doi.org/10.13039/501100000780 Framework Programme Seven 631396

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 Elsevier
publisher.none.fl_str_mv Elsevier
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
repository.name.fl_str_mv
repository.mail.fl_str_mv
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