Novel lawsone-containing ruthenium(II) complexes: Synthesis, characterization and anticancer activity on 2D and 3D spheroid models of prostate cancer cells
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Data
2019-04-01
Autores
De Grandis, Rone Aparecido [UNESP]
Silva dos Santos, Patrick Wellington da
Oliveira, Katia Mara de
Tomazela Machado, Ana Rita
Aissa, Alexandre Ferro
Batista, Alzir Azevedo
Greggi Antunes, Lusania Maria
Pavan, Fernando Rogerio [UNESP]
Título da Revista
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Editor
Elsevier B.V.
Resumo
This study describes a series of newly synthesized phosphine/diimine ruthenium complexes containing the lawsone as bioligand with enhanced cytotoxicity against different cancer cells, and apoptosis induction in prostatic cancer cells DU-145. The complexes [Ru(law)(N-N)(2)]PF6 where N-N is 2,2'-bipyridine (1) or 1,10-phenanthroline (2) and [Ru(law)(dppm)(N-N)]PF6, where dppm means bis(diphenylphosphino)methane, N-N is 2,2'-bipyridine (3) or 1,10-phenanthroline (4), and law is lawsone, were synthesized and fully characterized by elemental analysis, molar conductivity, NMR, UV-vis, IR spectroscopies and cyclic voltammetry. The interaction of the complexes (1-4) with DNA was evaluated by circular dichroism, gel electrophoresis, and fluorescence, and the complexes presented interactions by the minor grooves DNA. The phosphinic series of complexes exhibited a remarkably broad spectrum of anticancer activity with approximately 34-fold higher than cisplatin and 5-fold higher than doxorubicin, inhibiting the growth of 3D tumor spheroids and the ability to retain the colony survival of DU-145 cells. Also, the complex (4) inhibits DU-145 cell adhesion and migration potential indicating antimetastatic properties. The mechanism of its anticancer activity was found to be related to increased reactive oxygen species (ROS) generation, increased the BAX/BCL-2 ratio and subsequent apoptosis induction. Overall, these findings suggested that the complex (4) could be a promising candidate for further evaluation as a chemotherapeutic agent in the prostate cancer treatment.
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Palavras-chave
Cancer, 1,4-naphthoquinone, 3D-cell culture, ROS, Apoptosis, BAX/BCL-2
Como citar
Bioorganic Chemistry. San Diego: Academic Press Inc Elsevier Science, v. 85, p. 455-468, 2019.