6-Methoxyquinoline complexes as lung carcinoma agents: induction of oxidative damage on A549 monolayer and multicellular spheroid model

dc.creatorCadavid Vargas, Juan Fernando
dc.creatorVilla Pérez, Cristian
dc.creatorRuiz, María Carolina
dc.creatorLeón, Ignacio Esteban
dc.creatorValencia Uribe, Gloria Cristina
dc.creatorSoria, Delia Beatriz
dc.creatorEtcheverry, Susana Beatriz
dc.creatorDi Virgilio, Ana Laura
dc.date2019-03
dc.date2021-11-29T14:16:26Z
dc.date.accessioned2023-07-15T04:03:01Z
dc.date.available2023-07-15T04:03:01Z
dc.identifierhttp://sedici.unlp.edu.ar/handle/10915/128784
dc.identifierissn:1432-1327
dc.identifierissn:0949-8257
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/7468059
dc.descriptionThe 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.
dc.descriptionFacultad de Ciencias Exactas
dc.descriptionCentro de Química Inorgánica
dc.formatapplication/pdf
dc.format271-285
dc.languageen
dc.rightshttp://creativecommons.org/licenses/by-nc-sa/4.0/
dc.rightsCreative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)
dc.subjectCiencias Exactas
dc.subjectQuímica
dc.subject6-Methoxyquinoline complexes
dc.subjectLung carcinoma
dc.subjectA549 cells
dc.subjectMulticellular spheroid model
dc.subjectOxidative damage
dc.title6-Methoxyquinoline complexes as lung carcinoma agents: induction of oxidative damage on A549 monolayer and multicellular spheroid model
dc.typeArticulo
dc.typeArticulo


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