Artículo
Cu(II)-acylhydrazone complex, a potent and selective antitumor agent against human osteosarcoma: Mechanism of action studies over in vitro and in vivo models
Balsa, Lucia Mariana
; Solernó, Luisina María
; Rodríguez, María Rosa
; Parajón Costa, Beatriz Susana
; Gonzalez Baro, Ana Cecilia
; Alonso, Daniel Fernando
; Garona, Juan
; Leon, Ignacio Esteban
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Fecha de publicación:
10/2023
Editorial:
Elsevier Ireland
Revista:
Chemico-biological Interactions
ISSN:
0009-2797
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
Osteosarcoma (OS) is a frequent bone cancer, affecting largely children and young adults. Cisplatin (CDDP) has been efficacious in the treatment of different cancer such us OS but the development of chemoresistance and important side effects leading to therapeutic failure. Novel therapies including copper compounds have shown to be potentially effective as anticancer drugs and one alternative to usually employed platinum compounds. The goal of this work is the evaluation of the in vitro and in vivo antitumoral activity and dilucidate the molecular target of a Cu(II) cationic complex containing a tridentate hydrazone ligand, CuHL for short, H2L=N'-'-(2-hydroxy-3-methoxybenzylidene)thiophene-2-carbohydrazide, against human OS MG-63 cells. Anticancer activity on MG-63 cell line was evaluated in OS monolayer and spheroids. CuHL significantly impaired cell viability in both models (IC50 2D: 2.1 ± 0.3 μM; 3D: 9.1 ± 1.0 μM) (p < 0.001). Additional cell studies demonstrated the copper compound inhibits cell proliferation and conveys cells to apoptosis, determined by flow cytometry. CuHL showed a great genotoxicity, evaluated by comet assay. Proteomic analysis by Orbitrap Mass Spectometry identified 27 differentially expressed proteins: 17 proteins were found overexpressed and 10 underexpressed in MG-63 cells after the CuHL treatment. The response to unfolded protein was the most affected biological process. In addition, in vivo antitumor effects of the compound were evaluated on human OS tumors xenografted in nude mice. CuHL treatment, at a dose of 2 mg/kg i.p., given three times/week for one month, significantly inhibited the progression of OS xenografts and was associated to a reduction in mitotic index and to an increment of tumor necrosis (p < 0.01). Administration of standard-of-care cytotoxic agent CDDP, following the same treatment schedule as CuHL, failed to impair OS growth and progression.
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Articulos(CEQUINOR)
Articulos de CENTRO DE QUIMICA INORGANICA "DR. PEDRO J. AYMONINO"
Articulos de CENTRO DE QUIMICA INORGANICA "DR. PEDRO J. AYMONINO"
Citación
Balsa, Lucia Mariana; Solernó, Luisina María; Rodríguez, María Rosa; Parajón Costa, Beatriz Susana; Gonzalez Baro, Ana Cecilia; et al.; Cu(II)-acylhydrazone complex, a potent and selective antitumor agent against human osteosarcoma: Mechanism of action studies over in vitro and in vivo models; Elsevier Ireland; Chemico-biological Interactions; 384; 10-2023; 1-10
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