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Therapeutic potential of vanadium complexes with 1,10-phenanthroline ligands, quo vadis? Fate of complexes in cell media and cancer cells

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Resumo:(VO)-O-IV-complexes formulated as [(VO)-O-IV(OSO3)(phen)(2)] (1) (phen = 1,10-phenanthroline), [(VO)-O-IV(OSO3) (Me(2)phen)(2)] (2) (Me(2)phen = 4,7-dimethyl-1,10-phenanthroline) and [(VO)-O-IV(OSO3)(amphen)(2)] (3) (amphen = 5-amino-1,10-phenanthroline) were prepared and stability in cell incubation media evaluated. Their cytotoxicity was determined against the A2780 (ovarian), MCF7 (breast) and PC3 (prostate) human cancer cells at different incubation times. While at 3 and 24 h the cytotoxicity differs for complexes and corresponding free ligands, at 72 h incubation all compounds are equally active presenting low IC50 values. Upon incubation of A2780 cells with 1-3, cellular distribution of vanadium in cytosol, membranes, nucleus and cytoskeleton, indicate that the uptake of V is low, particularly for 1, and that the uptake pattern depends on the ligand. Nuclear microscopic techniques are used for imaging and elemental quantification in whole PC3 cells incubated with 1. Once complexes are added to cell culture media, they decompose, and with time most V-IV oxidizes to V-V-species. Modeling of speciation when [(VO)-O-IV(OSO3)(phen)(2)] (1) is added to cell media is presented. At lower concentrations of 1, (VO)-O-IV- and phen-containing species are mainly bound to bovine serum albumin, while at higher concentrations [(VO)-O-IV (phen)n](2+)-complexes become relevant, being predicted that the species taken up and mechanisms of action operating depend on the total concentration of complex. This study emphasizes that for these (VO)-O-IV-systems, and probably for many others involving oxidovanadium or other labile metal complexes, it is not possible to identify active species or propose mechanisms of cytotoxic action without evaluating speciation occurring in cell media.
Autores principais:Nunes, Patrique
Outros Autores:Correia, Isabel; Cavaco, Isabel; Marques, Fernanda; Pinheiro, Teresa; Avecilla, Fernando; Pessoa, Joao Costa
Assunto:Vanadium complexes 1,10-phenanthroline Cytotoxicity Speciation Cell incubation media Cell uptake
Ano:2021
País:Portugal
Tipo de documento:artigo
Tipo de acesso:acesso restrito
Instituição associada:Universidade do Algarve
Idioma:inglês
Origem:Sapientia - Universidade do Algarve

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