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...
| Autores: | , , , |
|---|---|
| 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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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 |
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info:eu-repo/semantics/openAccess |
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open access http://purl.org/coar/access_right/c_abf2 |
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openAccess |
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application/pdf |
| dc.publisher.none.fl_str_mv |
Elsevier |
| publisher.none.fl_str_mv |
Elsevier |
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reponame:Biblos-e Archivo. Repositorio Institucional de la UAM instname:Universidad Autónoma de Madrid |
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Universidad Autónoma de Madrid |
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Biblos-e Archivo. Repositorio Institucional de la UAM |
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Biblos-e Archivo. Repositorio Institucional de la UAM |
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15,301603 |