Screening and preliminary biochemical and biological studies of [RuCl(p-cymene)(N, N-bis(diphenylphosphino)-isopropylamine)][BF4] in Breast Cancer Models

Breast cancer is the second leading cause of cancer death worldwide. Despite progress in drug discovery, identification of the correct population is the limiting factor to develop new compounds in the clinical setting. Therefore, the aim of this study is to evaluate the effects of a new metallodrug,...

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Detalles Bibliográficos
Autores: Corrales Sánchez, Verónica, Nieto-Jiménez, Cristina, Castro-Osma, José Antonio, De Andrés, Fernando, Pacheco-Liñán, Pedro J., Bravo, Iván, Rodríguez Fariñas, Nuria, Niza, E., Domínguez-Jurado, Elena, Lara-Sánchez, Agustín, Ríos, Ángel, Gómez-Juárez, Mónica, Montero, Juan Carlos, Pandiella, Atanasio, Shafir, Alexandr, Alonso-Moreno, Carlos, Ocaña, Alberto
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2019
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/200659
Acceso en línea:http://hdl.handle.net/10261/200659
Access Level:acceso abierto
Palabra clave:Ruthenium
Coordination complexes
Ruthenium complexes
Descripción
Sumario:Breast cancer is the second leading cause of cancer death worldwide. Despite progress in drug discovery, identification of the correct population is the limiting factor to develop new compounds in the clinical setting. Therefore, the aim of this study is to evaluate the effects of a new metallodrug, [RuCl(p-cymene)(N,N-bis(diphenylphosphino)-isopropylamine)][BF4] (pnpRu-14), as a lead pnp-Ru compound by screening and preliminary biochemical and biological studies in different breast cancer subtypes. The results show that complex pnpRu-14 is much more effective in promoting in vitro cytotoxic effects on HER2+ and RH+/HER2- breast cancer than the reference metallodrugs cisplatin, carboplatin, or RAPTA-C. It is important to highlight that pnpRu-14 shows an impressive cytotoxicity against BT474 cells. Caspase-dependent apoptosis is the mechanism of action for these compounds. In addition, treatment of SKBR3, BT474, T47D, and MCF7 cancer cells with pnpRu-14 caused an accumulation of cells in the G0/G1 phase cells. The human serum albumin, DNA, and H1 histones binding properties of the lead compound are reported. Pharmacokinetic and biodistribution studies show a quick absorption of pnpRu-14 in serum with no significant accumulation in any of the tested organs. This work provides evidence to support the preclinical and clinical development of pnpRu-14 in breast cancer. Copyright © 2019 American Chemical Society.

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