Finding new molecular targets of two copper(II)-hydrazone complexes on triple-negative breast cancer cells using mass-spectrometry-based quantitative proteomics

Breast cancer is the most common cancer in women, with a high incidence estimated to reach 2.3 million by 2030. Triple-Negative Breast Cancer (TNBC) is the greatest invasive class of breast cancer with a poor prognosis, due to the side-effects exerted by the chemotherapy used and the low effectivity...

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Autores principales: Balsa, Lucía Mariana, Rodríguez, María Rosa, Ferraresi Curotto, Verónica, Parajón Costa, Beatriz Susana, González Baró, Ana Cecilia, León, Ignacio Esteban
Formato: Articulo
Lenguaje:Inglés
Publicado: 2023
Materias:
Biología
Ciencias Médicas
Breast cancer
Molecular targets
Metallodrugs
Copper(II)
Proteomics
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/152354
Aporte de:
SEDICI (UNLP) de Universidad Nacional de La Plata
id I19-R120-10915-152354
record_format dspace
spelling I19-R120-10915-1523542023-05-02T20:07:39Z http://sedici.unlp.edu.ar/handle/10915/152354 issn:1422-0067 Finding new molecular targets of two copper(II)-hydrazone complexes on triple-negative breast cancer cells using mass-spectrometry-based quantitative proteomics Balsa, Lucía Mariana Rodríguez, María Rosa Ferraresi Curotto, Verónica Parajón Costa, Beatriz Susana González Baró, Ana Cecilia León, Ignacio Esteban 2023 2023-05-02T18:17:32Z en Biología Ciencias Médicas Breast cancer Molecular targets Metallodrugs Copper(II) Proteomics Breast cancer is the most common cancer in women, with a high incidence estimated to reach 2.3 million by 2030. Triple-Negative Breast Cancer (TNBC) is the greatest invasive class of breast cancer with a poor prognosis, due to the side-effects exerted by the chemotherapy used and the low effectivity of novel treatments. In this sense, copper compounds have shown to be potentially effective as antitumor agents, attracting increasing interest as alternatives to the usually employed platinum-derived drugs. Therefore, the aim of this work is to identify differentially expressed proteins in MDA-MB-231 cells exposed to two copper(II)-hydrazone complexes using label-free quantitative proteomics and functional bioinformatics strategies to identify the molecular mechanisms through which these copper complexes exert their antitumoral effect in TNBC cells. Both copper complexes increased proteins involved in endoplasmic reticulum stress and unfolded protein response, as well as the downregulation of proteins related to DNA replication and repair. One of the most relevant anticancer mechanisms of action found for CuHL1 and CuHL2 was the down-regulation of gain-offunction- mutant p53. Moreover, we found a novel and interesting effect for a copper metallodrug, which was the down-regulation of proteins related to lipid synthesis and metabolism that could lead to a beneficial decrease in lipid levels. Centro de Química Inorgánica Instituto de Física La Plata Articulo Articulo http://creativecommons.org/licenses/by/4.0/ Creative Commons Attribution 4.0 International (CC BY 4.0) application/pdf
institution Universidad Nacional de La Plata
institution_str I-19
repository_str R-120
collection SEDICI (UNLP)
language Inglés
topic Biología
Ciencias Médicas
Breast cancer
Molecular targets
Metallodrugs
Copper(II)
Proteomics
spellingShingle Biología
Ciencias Médicas
Breast cancer
Molecular targets
Metallodrugs
Copper(II)
Proteomics
Balsa, Lucía Mariana
Rodríguez, María Rosa
Ferraresi Curotto, Verónica
Parajón Costa, Beatriz Susana
González Baró, Ana Cecilia
León, Ignacio Esteban
Finding new molecular targets of two copper(II)-hydrazone complexes on triple-negative breast cancer cells using mass-spectrometry-based quantitative proteomics
topic_facet Biología
Ciencias Médicas
Breast cancer
Molecular targets
Metallodrugs
Copper(II)
Proteomics
description Breast cancer is the most common cancer in women, with a high incidence estimated to reach 2.3 million by 2030. Triple-Negative Breast Cancer (TNBC) is the greatest invasive class of breast cancer with a poor prognosis, due to the side-effects exerted by the chemotherapy used and the low effectivity of novel treatments. In this sense, copper compounds have shown to be potentially effective as antitumor agents, attracting increasing interest as alternatives to the usually employed platinum-derived drugs. Therefore, the aim of this work is to identify differentially expressed proteins in MDA-MB-231 cells exposed to two copper(II)-hydrazone complexes using label-free quantitative proteomics and functional bioinformatics strategies to identify the molecular mechanisms through which these copper complexes exert their antitumoral effect in TNBC cells. Both copper complexes increased proteins involved in endoplasmic reticulum stress and unfolded protein response, as well as the downregulation of proteins related to DNA replication and repair. One of the most relevant anticancer mechanisms of action found for CuHL1 and CuHL2 was the down-regulation of gain-offunction- mutant p53. Moreover, we found a novel and interesting effect for a copper metallodrug, which was the down-regulation of proteins related to lipid synthesis and metabolism that could lead to a beneficial decrease in lipid levels.
format Articulo
Articulo
author Balsa, Lucía Mariana
Rodríguez, María Rosa
Ferraresi Curotto, Verónica
Parajón Costa, Beatriz Susana
González Baró, Ana Cecilia
León, Ignacio Esteban
author_facet Balsa, Lucía Mariana
Rodríguez, María Rosa
Ferraresi Curotto, Verónica
Parajón Costa, Beatriz Susana
González Baró, Ana Cecilia
León, Ignacio Esteban
author_sort Balsa, Lucía Mariana
title Finding new molecular targets of two copper(II)-hydrazone complexes on triple-negative breast cancer cells using mass-spectrometry-based quantitative proteomics
title_short Finding new molecular targets of two copper(II)-hydrazone complexes on triple-negative breast cancer cells using mass-spectrometry-based quantitative proteomics
title_full Finding new molecular targets of two copper(II)-hydrazone complexes on triple-negative breast cancer cells using mass-spectrometry-based quantitative proteomics
title_fullStr Finding new molecular targets of two copper(II)-hydrazone complexes on triple-negative breast cancer cells using mass-spectrometry-based quantitative proteomics
title_full_unstemmed Finding new molecular targets of two copper(II)-hydrazone complexes on triple-negative breast cancer cells using mass-spectrometry-based quantitative proteomics
title_sort finding new molecular targets of two copper(ii)-hydrazone complexes on triple-negative breast cancer cells using mass-spectrometry-based quantitative proteomics
publishDate 2023
url http://sedici.unlp.edu.ar/handle/10915/152354
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