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Screening and Preliminary Biochemical and Biological Studies of [RuCl(p-cymene)(N,N-bis(diphenylphosphino)-isopropylamine)][BF(4)] in Breast Cancer Models
[Image: see text] 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...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Chemical Society
2019
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6704442/ https://www.ncbi.nlm.nih.gov/pubmed/31460427 http://dx.doi.org/10.1021/acsomega.9b00296 |
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author | Corrales Sánchez, Veronica Nieto-Jiménez, Cristina Castro-Osma, José Antonio de Andrés, Fernando Pacheco-Liñán, Pedro J. Bravo, Iván Rodríguez Fariñas, Nuria Niza, Enrique Domínguez-Jurado, Elena Lara-Sánchez, Agustín Ríos, Ángel Gómez Juárez, Mónica Montero, Juan Carlos Pandiella, Atanasio Shafir, Alexandr Alonso-Moreno, Carlos Ocaña, Alberto |
author_facet | Corrales Sánchez, Veronica Nieto-Jiménez, Cristina Castro-Osma, José Antonio de Andrés, Fernando Pacheco-Liñán, Pedro J. Bravo, Iván Rodríguez Fariñas, Nuria Niza, Enrique Domínguez-Jurado, Elena Lara-Sánchez, Agustín Ríos, Ángel Gómez Juárez, Mónica Montero, Juan Carlos Pandiella, Atanasio Shafir, Alexandr Alonso-Moreno, Carlos Ocaña, Alberto |
author_sort | Corrales Sánchez, Veronica |
collection | PubMed |
description | [Image: see text] 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)][BF(4)] (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. |
format | Online Article Text |
id | pubmed-6704442 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | American Chemical Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-67044422019-08-27 Screening and Preliminary Biochemical and Biological Studies of [RuCl(p-cymene)(N,N-bis(diphenylphosphino)-isopropylamine)][BF(4)] in Breast Cancer Models Corrales Sánchez, Veronica Nieto-Jiménez, Cristina Castro-Osma, José Antonio de Andrés, Fernando Pacheco-Liñán, Pedro J. Bravo, Iván Rodríguez Fariñas, Nuria Niza, Enrique Domínguez-Jurado, Elena Lara-Sánchez, Agustín Ríos, Ángel Gómez Juárez, Mónica Montero, Juan Carlos Pandiella, Atanasio Shafir, Alexandr Alonso-Moreno, Carlos Ocaña, Alberto ACS Omega [Image: see text] 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)][BF(4)] (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. American Chemical Society 2019-08-01 /pmc/articles/PMC6704442/ /pubmed/31460427 http://dx.doi.org/10.1021/acsomega.9b00296 Text en Copyright © 2019 American Chemical Society This is an open access article published under an ACS AuthorChoice License (http://pubs.acs.org/page/policy/authorchoice_termsofuse.html) , which permits copying and redistribution of the article or any adaptations for non-commercial purposes. |
spellingShingle | Corrales Sánchez, Veronica Nieto-Jiménez, Cristina Castro-Osma, José Antonio de Andrés, Fernando Pacheco-Liñán, Pedro J. Bravo, Iván Rodríguez Fariñas, Nuria Niza, Enrique Domínguez-Jurado, Elena Lara-Sánchez, Agustín Ríos, Ángel Gómez Juárez, Mónica Montero, Juan Carlos Pandiella, Atanasio Shafir, Alexandr Alonso-Moreno, Carlos Ocaña, Alberto Screening and Preliminary Biochemical and Biological Studies of [RuCl(p-cymene)(N,N-bis(diphenylphosphino)-isopropylamine)][BF(4)] in Breast Cancer Models |
title | Screening and Preliminary Biochemical and Biological
Studies of [RuCl(p-cymene)(N,N-bis(diphenylphosphino)-isopropylamine)][BF(4)] in Breast Cancer Models |
title_full | Screening and Preliminary Biochemical and Biological
Studies of [RuCl(p-cymene)(N,N-bis(diphenylphosphino)-isopropylamine)][BF(4)] in Breast Cancer Models |
title_fullStr | Screening and Preliminary Biochemical and Biological
Studies of [RuCl(p-cymene)(N,N-bis(diphenylphosphino)-isopropylamine)][BF(4)] in Breast Cancer Models |
title_full_unstemmed | Screening and Preliminary Biochemical and Biological
Studies of [RuCl(p-cymene)(N,N-bis(diphenylphosphino)-isopropylamine)][BF(4)] in Breast Cancer Models |
title_short | Screening and Preliminary Biochemical and Biological
Studies of [RuCl(p-cymene)(N,N-bis(diphenylphosphino)-isopropylamine)][BF(4)] in Breast Cancer Models |
title_sort | screening and preliminary biochemical and biological
studies of [rucl(p-cymene)(n,n-bis(diphenylphosphino)-isopropylamine)][bf(4)] in breast cancer models |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6704442/ https://www.ncbi.nlm.nih.gov/pubmed/31460427 http://dx.doi.org/10.1021/acsomega.9b00296 |
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