A Pt(IV) Prodrug Combining Chlorambucil and Cisplatin: A Dual-Acting Weapon for Targeting DNA in Cancer Cells

In this study, two DNA-targeting agents, cisplatin and chlorambucil, were combined in a Pt(IV) prodrug, 1, which was thoroughly characterized by means of spectroscopic and spectrometric techniques. Tested towards a panel of various human tumor cell lines, this compound showed superior in vitro antit...

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Autores principales: Montagner, Diego, Tolan, Dina, Andriollo, Emma, Gandin, Valentina, Marzano, Cristina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6321036/
https://www.ncbi.nlm.nih.gov/pubmed/30486477
http://dx.doi.org/10.3390/ijms19123775
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author Montagner, Diego
Tolan, Dina
Andriollo, Emma
Gandin, Valentina
Marzano, Cristina
author_facet Montagner, Diego
Tolan, Dina
Andriollo, Emma
Gandin, Valentina
Marzano, Cristina
author_sort Montagner, Diego
collection PubMed
description In this study, two DNA-targeting agents, cisplatin and chlorambucil, were combined in a Pt(IV) prodrug, 1, which was thoroughly characterized by means of spectroscopic and spectrometric techniques. Tested towards a panel of various human tumor cell lines, this compound showed superior in vitro antitumor potential than the reference drug cisplatin. In addition, an antitumor potential of 1 was found, which is comparable to that of oxaliplatin in 3D spheroid models of colon cancer cells. Mechanistic studies performed in colon cancer cells confirmed that the conjugation of chlorambucil to Pt(IV) cisplatin-based scaffold tunes the lipophilicity of the prodrug, consequently improving the ability of the compound to accumulate into cancer cells and to target DNA, ultimately leading to apoptotic cancer cell death.
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spelling pubmed-63210362019-01-07 A Pt(IV) Prodrug Combining Chlorambucil and Cisplatin: A Dual-Acting Weapon for Targeting DNA in Cancer Cells Montagner, Diego Tolan, Dina Andriollo, Emma Gandin, Valentina Marzano, Cristina Int J Mol Sci Article In this study, two DNA-targeting agents, cisplatin and chlorambucil, were combined in a Pt(IV) prodrug, 1, which was thoroughly characterized by means of spectroscopic and spectrometric techniques. Tested towards a panel of various human tumor cell lines, this compound showed superior in vitro antitumor potential than the reference drug cisplatin. In addition, an antitumor potential of 1 was found, which is comparable to that of oxaliplatin in 3D spheroid models of colon cancer cells. Mechanistic studies performed in colon cancer cells confirmed that the conjugation of chlorambucil to Pt(IV) cisplatin-based scaffold tunes the lipophilicity of the prodrug, consequently improving the ability of the compound to accumulate into cancer cells and to target DNA, ultimately leading to apoptotic cancer cell death. MDPI 2018-11-27 /pmc/articles/PMC6321036/ /pubmed/30486477 http://dx.doi.org/10.3390/ijms19123775 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Montagner, Diego
Tolan, Dina
Andriollo, Emma
Gandin, Valentina
Marzano, Cristina
A Pt(IV) Prodrug Combining Chlorambucil and Cisplatin: A Dual-Acting Weapon for Targeting DNA in Cancer Cells
title A Pt(IV) Prodrug Combining Chlorambucil and Cisplatin: A Dual-Acting Weapon for Targeting DNA in Cancer Cells
title_full A Pt(IV) Prodrug Combining Chlorambucil and Cisplatin: A Dual-Acting Weapon for Targeting DNA in Cancer Cells
title_fullStr A Pt(IV) Prodrug Combining Chlorambucil and Cisplatin: A Dual-Acting Weapon for Targeting DNA in Cancer Cells
title_full_unstemmed A Pt(IV) Prodrug Combining Chlorambucil and Cisplatin: A Dual-Acting Weapon for Targeting DNA in Cancer Cells
title_short A Pt(IV) Prodrug Combining Chlorambucil and Cisplatin: A Dual-Acting Weapon for Targeting DNA in Cancer Cells
title_sort pt(iv) prodrug combining chlorambucil and cisplatin: a dual-acting weapon for targeting dna in cancer cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6321036/
https://www.ncbi.nlm.nih.gov/pubmed/30486477
http://dx.doi.org/10.3390/ijms19123775
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