6-Methoxyquinoline complexes as lung carcinoma agents: induction of oxidative damage on A549 monolayer and multicellular spheroid model
- Autores
- Cadavid Vargas, Juan Fernando; Villa Pérez, Cristian; Ruiz, María Carolina; León, Ignacio Esteban; Valencia Uribe, Gloria Cristina; Soria, Delia Beatriz; Etcheverry, Susana Beatriz; Di Virgilio, Ana Laura
- Año de publicación
- 2019
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- The aim of this work was to study the antitumor effects and the mechanisms of toxic action of a series of 6-methoxyquinoline (6MQ) complexes in vitro. The Cu(II) and Zn(II) complexes (Cu6MQ and Zn6MQ) are formulated as M(6MQ)₂Cl₂; the Co(II) and Ag(I) compounds (Co6MQ and Ag6MQ) are ionic with formulae [Ag(6MQ)₂]⁺NO₃⁻ and H(6MQ)⁺[Co(6MQ)Cl₃]⁻ (where H(6MQ)⁺ is the protonated ligand). We found that the copper complex, outperformed the Co(II), Zn(II) and Ag(I) complexes with a lower IC₅₀ (57.9 µM) in A549 cells exposed for 24 h. Cu6MQ decreased cell proliferation and induced oxidative stress detected with H₂DCFDA at 40 µM, which reduces GSH/GSSG ratio. This redox imbalance induced oxidative DNA damage revealed by the Micronucleus test and the Comet assay, which turned into a cell cycle arrest at G2/M phase and induced apoptosis. In multicellular spheroids, the IC₅₀ values tripled the monolayer model (187.3 µM for 24 h). At this concentration, the proportion of live/dead cells diminished, and the spheroids could not proliferate or invade. Although Zn6MQ also decreased GSH/GSSG ratio from 200 µM and the cytotoxicity is related to oxidative stress, the induction of the hydrogen peroxide levels only doubled the control value. Zn6MQ induced S phase arrest, which relates with the increased micronucleus frequency and with the induction of necrosis. Finally, our results reveal a synergistic activity with a 1:1 ratio of both complexes in the monolayer and multicellular spheroids.
Facultad de Ciencias Exactas
Centro de Química Inorgánica - Materia
-
Ciencias Exactas
Química
6-Methoxyquinoline complexes
Lung carcinoma
A549 cells
Multicellular spheroid model
Oxidative damage - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- http://creativecommons.org/licenses/by-nc-sa/4.0/
- Repositorio
.jpg)
- Institución
- Universidad Nacional de La Plata
- OAI Identificador
- oai:sedici.unlp.edu.ar:10915/128784
Ver los metadatos del registro completo
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6-Methoxyquinoline complexes as lung carcinoma agents: induction of oxidative damage on A549 monolayer and multicellular spheroid modelCadavid Vargas, Juan FernandoVilla Pérez, CristianRuiz, María CarolinaLeón, Ignacio EstebanValencia Uribe, Gloria CristinaSoria, Delia BeatrizEtcheverry, Susana BeatrizDi Virgilio, Ana LauraCiencias ExactasQuímica6-Methoxyquinoline complexesLung carcinomaA549 cellsMulticellular spheroid modelOxidative damageThe aim of this work was to study the antitumor effects and the mechanisms of toxic action of a series of 6-methoxyquinoline (6MQ) complexes in vitro. The Cu(II) and Zn(II) complexes (Cu6MQ and Zn6MQ) are formulated as M(6MQ)₂Cl₂; the Co(II) and Ag(I) compounds (Co6MQ and Ag6MQ) are ionic with formulae [Ag(6MQ)₂]⁺NO₃⁻ and H(6MQ)⁺[Co(6MQ)Cl₃]⁻ (where H(6MQ)⁺ is the protonated ligand). We found that the copper complex, outperformed the Co(II), Zn(II) and Ag(I) complexes with a lower IC₅₀ (57.9 µM) in A549 cells exposed for 24 h. Cu6MQ decreased cell proliferation and induced oxidative stress detected with H₂DCFDA at 40 µM, which reduces GSH/GSSG ratio. This redox imbalance induced oxidative DNA damage revealed by the Micronucleus test and the Comet assay, which turned into a cell cycle arrest at G2/M phase and induced apoptosis. In multicellular spheroids, the IC₅₀ values tripled the monolayer model (187.3 µM for 24 h). At this concentration, the proportion of live/dead cells diminished, and the spheroids could not proliferate or invade. Although Zn6MQ also decreased GSH/GSSG ratio from 200 µM and the cytotoxicity is related to oxidative stress, the induction of the hydrogen peroxide levels only doubled the control value. Zn6MQ induced S phase arrest, which relates with the increased micronucleus frequency and with the induction of necrosis. Finally, our results reveal a synergistic activity with a 1:1 ratio of both complexes in the monolayer and multicellular spheroids.Facultad de Ciencias ExactasCentro de Química Inorgánica2019-03info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionArticulohttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdf271-285http://sedici.unlp.edu.ar/handle/10915/128784enginfo:eu-repo/semantics/altIdentifier/issn/1432-1327info:eu-repo/semantics/altIdentifier/issn/0949-8257info:eu-repo/semantics/altIdentifier/pmid/30701359info:eu-repo/semantics/altIdentifier/doi/10.1007/s00775-019-01644-7info:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by-nc-sa/4.0/Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)reponame:SEDICI (UNLP)instname:Universidad Nacional de La Platainstacron:UNLP2025-10-15T11:22:49Zoai:sedici.unlp.edu.ar:10915/128784Institucionalhttp://sedici.unlp.edu.ar/Universidad públicaNo correspondehttp://sedici.unlp.edu.ar/oai/snrdalira@sedici.unlp.edu.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:13292025-10-15 11:22:50.273SEDICI (UNLP) - Universidad Nacional de La Platafalse |
| dc.title.none.fl_str_mv |
6-Methoxyquinoline complexes as lung carcinoma agents: induction of oxidative damage on A549 monolayer and multicellular spheroid model |
| title |
6-Methoxyquinoline complexes as lung carcinoma agents: induction of oxidative damage on A549 monolayer and multicellular spheroid model |
| spellingShingle |
6-Methoxyquinoline complexes as lung carcinoma agents: induction of oxidative damage on A549 monolayer and multicellular spheroid model Cadavid Vargas, Juan Fernando Ciencias Exactas Química 6-Methoxyquinoline complexes Lung carcinoma A549 cells Multicellular spheroid model Oxidative damage |
| title_short |
6-Methoxyquinoline complexes as lung carcinoma agents: induction of oxidative damage on A549 monolayer and multicellular spheroid model |
| title_full |
6-Methoxyquinoline complexes as lung carcinoma agents: induction of oxidative damage on A549 monolayer and multicellular spheroid model |
| title_fullStr |
6-Methoxyquinoline complexes as lung carcinoma agents: induction of oxidative damage on A549 monolayer and multicellular spheroid model |
| title_full_unstemmed |
6-Methoxyquinoline complexes as lung carcinoma agents: induction of oxidative damage on A549 monolayer and multicellular spheroid model |
| title_sort |
6-Methoxyquinoline complexes as lung carcinoma agents: induction of oxidative damage on A549 monolayer and multicellular spheroid model |
| dc.creator.none.fl_str_mv |
Cadavid Vargas, Juan Fernando Villa Pérez, Cristian Ruiz, María Carolina León, Ignacio Esteban Valencia Uribe, Gloria Cristina Soria, Delia Beatriz Etcheverry, Susana Beatriz Di Virgilio, Ana Laura |
| author |
Cadavid Vargas, Juan Fernando |
| author_facet |
Cadavid Vargas, Juan Fernando Villa Pérez, Cristian Ruiz, María Carolina León, Ignacio Esteban Valencia Uribe, Gloria Cristina Soria, Delia Beatriz Etcheverry, Susana Beatriz Di Virgilio, Ana Laura |
| author_role |
author |
| author2 |
Villa Pérez, Cristian Ruiz, María Carolina León, Ignacio Esteban Valencia Uribe, Gloria Cristina Soria, Delia Beatriz Etcheverry, Susana Beatriz Di Virgilio, Ana Laura |
| author2_role |
author author author author author author author |
| dc.subject.none.fl_str_mv |
Ciencias Exactas Química 6-Methoxyquinoline complexes Lung carcinoma A549 cells Multicellular spheroid model Oxidative damage |
| topic |
Ciencias Exactas Química 6-Methoxyquinoline complexes Lung carcinoma A549 cells Multicellular spheroid model Oxidative damage |
| dc.description.none.fl_txt_mv |
The aim of this work was to study the antitumor effects and the mechanisms of toxic action of a series of 6-methoxyquinoline (6MQ) complexes in vitro. The Cu(II) and Zn(II) complexes (Cu6MQ and Zn6MQ) are formulated as M(6MQ)₂Cl₂; the Co(II) and Ag(I) compounds (Co6MQ and Ag6MQ) are ionic with formulae [Ag(6MQ)₂]⁺NO₃⁻ and H(6MQ)⁺[Co(6MQ)Cl₃]⁻ (where H(6MQ)⁺ is the protonated ligand). We found that the copper complex, outperformed the Co(II), Zn(II) and Ag(I) complexes with a lower IC₅₀ (57.9 µM) in A549 cells exposed for 24 h. Cu6MQ decreased cell proliferation and induced oxidative stress detected with H₂DCFDA at 40 µM, which reduces GSH/GSSG ratio. This redox imbalance induced oxidative DNA damage revealed by the Micronucleus test and the Comet assay, which turned into a cell cycle arrest at G2/M phase and induced apoptosis. In multicellular spheroids, the IC₅₀ values tripled the monolayer model (187.3 µM for 24 h). At this concentration, the proportion of live/dead cells diminished, and the spheroids could not proliferate or invade. Although Zn6MQ also decreased GSH/GSSG ratio from 200 µM and the cytotoxicity is related to oxidative stress, the induction of the hydrogen peroxide levels only doubled the control value. Zn6MQ induced S phase arrest, which relates with the increased micronucleus frequency and with the induction of necrosis. Finally, our results reveal a synergistic activity with a 1:1 ratio of both complexes in the monolayer and multicellular spheroids. Facultad de Ciencias Exactas Centro de Química Inorgánica |
| description |
The aim of this work was to study the antitumor effects and the mechanisms of toxic action of a series of 6-methoxyquinoline (6MQ) complexes in vitro. The Cu(II) and Zn(II) complexes (Cu6MQ and Zn6MQ) are formulated as M(6MQ)₂Cl₂; the Co(II) and Ag(I) compounds (Co6MQ and Ag6MQ) are ionic with formulae [Ag(6MQ)₂]⁺NO₃⁻ and H(6MQ)⁺[Co(6MQ)Cl₃]⁻ (where H(6MQ)⁺ is the protonated ligand). We found that the copper complex, outperformed the Co(II), Zn(II) and Ag(I) complexes with a lower IC₅₀ (57.9 µM) in A549 cells exposed for 24 h. Cu6MQ decreased cell proliferation and induced oxidative stress detected with H₂DCFDA at 40 µM, which reduces GSH/GSSG ratio. This redox imbalance induced oxidative DNA damage revealed by the Micronucleus test and the Comet assay, which turned into a cell cycle arrest at G2/M phase and induced apoptosis. In multicellular spheroids, the IC₅₀ values tripled the monolayer model (187.3 µM for 24 h). At this concentration, the proportion of live/dead cells diminished, and the spheroids could not proliferate or invade. Although Zn6MQ also decreased GSH/GSSG ratio from 200 µM and the cytotoxicity is related to oxidative stress, the induction of the hydrogen peroxide levels only doubled the control value. Zn6MQ induced S phase arrest, which relates with the increased micronucleus frequency and with the induction of necrosis. Finally, our results reveal a synergistic activity with a 1:1 ratio of both complexes in the monolayer and multicellular spheroids. |
| publishDate |
2019 |
| dc.date.none.fl_str_mv |
2019-03 |
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info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Articulo http://purl.org/coar/resource_type/c_6501 info:ar-repo/semantics/articulo |
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article |
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eng |
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eng |
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openAccess |
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http://creativecommons.org/licenses/by-nc-sa/4.0/ Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) |
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