Deciphering the effect of a Cu(II)‐hydrazone complex on intracellular cell signalling pathways in a human osteosarcoma 2D and 3D models

Autores
Balsa, Lucia Mariana; Santa Maria de la Parra, Lucía; Ferretti, Valeria; Leon, Ignacio Esteban
Año de publicación
2024
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
New therapeutic strategies for osteosarcoma (OS) have demonstrated the potential efficacy of copper compounds as anticancer drugs and as a substitute for the often used platinum compounds. OS is a type of bone cancer, primarily affecting young adults and children..The main objective of this work is to discover the molecular targets and cellular pathways related to the antitumor properties of a Cu(II)-hydrazone toward human OS 2D and 3D systems. Cell viability study using MG-63 cells was evaluated in OS monolayer and spheroids. CuHL significantly reduced cell viability in OS models (IC50 2D: 2.6 ± 0.3 µM; IC50 3D: 9.9 ± 1.4 µM) (p<0.001). Also, CuHL inhibits cell proliferation and it induces cells to apoptosis. The main mechanism of action found for CuHL are the interaction with DNA, genotoxicity, the ROS generation and the proteasome activity inhibition. Besides, 67 differentially expressed proteins were found using proteomic approaches. Of those 67 proteins, 40 were found overexpressed and 27 underexpressed. The response to stress and to unfolded protein, as well as ATP synthesis were the most affected biological process among upregulated proteins, whilst proteins related to DNA replication and redox homeostasis were downregulated.
Fil: Balsa, Lucia Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; Argentina
Fil: Santa Maria de la Parra, Lucía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; Argentina
Fil: Ferretti, Valeria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; Argentina
Fil: Leon, Ignacio Esteban. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; Argentina
Materia
COPPER COMPLEX
CELL SIGNALLING PATHWAYS
OSTEOSARCOMA
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/265096
Acceder
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network_acronym_str CONICETDig
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network_name_str CONICET Digital (CONICET)
spelling Deciphering the effect of a Cu(II)‐hydrazone complex on intracellular cell signalling pathways in a human osteosarcoma 2D and 3D modelsBalsa, Lucia MarianaSanta Maria de la Parra, LucíaFerretti, ValeriaLeon, Ignacio EstebanCOPPER COMPLEXCELL SIGNALLING PATHWAYSOSTEOSARCOMAhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1New therapeutic strategies for osteosarcoma (OS) have demonstrated the potential efficacy of copper compounds as anticancer drugs and as a substitute for the often used platinum compounds. OS is a type of bone cancer, primarily affecting young adults and children..The main objective of this work is to discover the molecular targets and cellular pathways related to the antitumor properties of a Cu(II)-hydrazone toward human OS 2D and 3D systems. Cell viability study using MG-63 cells was evaluated in OS monolayer and spheroids. CuHL significantly reduced cell viability in OS models (IC50 2D: 2.6 ± 0.3 µM; IC50 3D: 9.9 ± 1.4 µM) (p<0.001). Also, CuHL inhibits cell proliferation and it induces cells to apoptosis. The main mechanism of action found for CuHL are the interaction with DNA, genotoxicity, the ROS generation and the proteasome activity inhibition. Besides, 67 differentially expressed proteins were found using proteomic approaches. Of those 67 proteins, 40 were found overexpressed and 27 underexpressed. The response to stress and to unfolded protein, as well as ATP synthesis were the most affected biological process among upregulated proteins, whilst proteins related to DNA replication and redox homeostasis were downregulated.Fil: Balsa, Lucia Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; ArgentinaFil: Santa Maria de la Parra, Lucía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; ArgentinaFil: Ferretti, Valeria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; ArgentinaFil: Leon, Ignacio Esteban. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; ArgentinaWiley VCH Verlag2024-08info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/265096Balsa, Lucia Mariana; Santa Maria de la Parra, Lucía; Ferretti, Valeria; Leon, Ignacio Esteban; Deciphering the effect of a Cu(II)‐hydrazone complex on intracellular cell signalling pathways in a human osteosarcoma 2D and 3D models; Wiley VCH Verlag; Chembiochem; 8-2024; 1-161439-4227CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://chemistry-europe.onlinelibrary.wiley.com/doi/10.1002/cbic.202400373info:eu-repo/semantics/altIdentifier/doi/10.1002/cbic.202400373info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-10T13:01:34Zoai:ri.conicet.gov.ar:11336/265096instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-10 13:01:34.701CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Deciphering the effect of a Cu(II)‐hydrazone complex on intracellular cell signalling pathways in a human osteosarcoma 2D and 3D models
title Deciphering the effect of a Cu(II)‐hydrazone complex on intracellular cell signalling pathways in a human osteosarcoma 2D and 3D models
spellingShingle Deciphering the effect of a Cu(II)‐hydrazone complex on intracellular cell signalling pathways in a human osteosarcoma 2D and 3D models
Balsa, Lucia Mariana
COPPER COMPLEX
CELL SIGNALLING PATHWAYS
OSTEOSARCOMA
title_short Deciphering the effect of a Cu(II)‐hydrazone complex on intracellular cell signalling pathways in a human osteosarcoma 2D and 3D models
title_full Deciphering the effect of a Cu(II)‐hydrazone complex on intracellular cell signalling pathways in a human osteosarcoma 2D and 3D models
title_fullStr Deciphering the effect of a Cu(II)‐hydrazone complex on intracellular cell signalling pathways in a human osteosarcoma 2D and 3D models
title_full_unstemmed Deciphering the effect of a Cu(II)‐hydrazone complex on intracellular cell signalling pathways in a human osteosarcoma 2D and 3D models
title_sort Deciphering the effect of a Cu(II)‐hydrazone complex on intracellular cell signalling pathways in a human osteosarcoma 2D and 3D models
dc.creator.none.fl_str_mv Balsa, Lucia Mariana
Santa Maria de la Parra, Lucía
Ferretti, Valeria
Leon, Ignacio Esteban
author Balsa, Lucia Mariana
author_facet Balsa, Lucia Mariana
Santa Maria de la Parra, Lucía
Ferretti, Valeria
Leon, Ignacio Esteban
author_role author
author2 Santa Maria de la Parra, Lucía
Ferretti, Valeria
Leon, Ignacio Esteban
author2_role author
author
author
dc.subject.none.fl_str_mv COPPER COMPLEX
CELL SIGNALLING PATHWAYS
OSTEOSARCOMA
topic COPPER COMPLEX
CELL SIGNALLING PATHWAYS
OSTEOSARCOMA
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv New therapeutic strategies for osteosarcoma (OS) have demonstrated the potential efficacy of copper compounds as anticancer drugs and as a substitute for the often used platinum compounds. OS is a type of bone cancer, primarily affecting young adults and children..The main objective of this work is to discover the molecular targets and cellular pathways related to the antitumor properties of a Cu(II)-hydrazone toward human OS 2D and 3D systems. Cell viability study using MG-63 cells was evaluated in OS monolayer and spheroids. CuHL significantly reduced cell viability in OS models (IC50 2D: 2.6 ± 0.3 µM; IC50 3D: 9.9 ± 1.4 µM) (p<0.001). Also, CuHL inhibits cell proliferation and it induces cells to apoptosis. The main mechanism of action found for CuHL are the interaction with DNA, genotoxicity, the ROS generation and the proteasome activity inhibition. Besides, 67 differentially expressed proteins were found using proteomic approaches. Of those 67 proteins, 40 were found overexpressed and 27 underexpressed. The response to stress and to unfolded protein, as well as ATP synthesis were the most affected biological process among upregulated proteins, whilst proteins related to DNA replication and redox homeostasis were downregulated.
Fil: Balsa, Lucia Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; Argentina
Fil: Santa Maria de la Parra, Lucía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; Argentina
Fil: Ferretti, Valeria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; Argentina
Fil: Leon, Ignacio Esteban. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; Argentina
description New therapeutic strategies for osteosarcoma (OS) have demonstrated the potential efficacy of copper compounds as anticancer drugs and as a substitute for the often used platinum compounds. OS is a type of bone cancer, primarily affecting young adults and children..The main objective of this work is to discover the molecular targets and cellular pathways related to the antitumor properties of a Cu(II)-hydrazone toward human OS 2D and 3D systems. Cell viability study using MG-63 cells was evaluated in OS monolayer and spheroids. CuHL significantly reduced cell viability in OS models (IC50 2D: 2.6 ± 0.3 µM; IC50 3D: 9.9 ± 1.4 µM) (p<0.001). Also, CuHL inhibits cell proliferation and it induces cells to apoptosis. The main mechanism of action found for CuHL are the interaction with DNA, genotoxicity, the ROS generation and the proteasome activity inhibition. Besides, 67 differentially expressed proteins were found using proteomic approaches. Of those 67 proteins, 40 were found overexpressed and 27 underexpressed. The response to stress and to unfolded protein, as well as ATP synthesis were the most affected biological process among upregulated proteins, whilst proteins related to DNA replication and redox homeostasis were downregulated.
publishDate 2024
dc.date.none.fl_str_mv 2024-08
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/265096
Balsa, Lucia Mariana; Santa Maria de la Parra, Lucía; Ferretti, Valeria; Leon, Ignacio Esteban; Deciphering the effect of a Cu(II)‐hydrazone complex on intracellular cell signalling pathways in a human osteosarcoma 2D and 3D models; Wiley VCH Verlag; Chembiochem; 8-2024; 1-16
1439-4227
CONICET Digital
CONICET
url http://hdl.handle.net/11336/265096
identifier_str_mv Balsa, Lucia Mariana; Santa Maria de la Parra, Lucía; Ferretti, Valeria; Leon, Ignacio Esteban; Deciphering the effect of a Cu(II)‐hydrazone complex on intracellular cell signalling pathways in a human osteosarcoma 2D and 3D models; Wiley VCH Verlag; Chembiochem; 8-2024; 1-16
1439-4227
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://chemistry-europe.onlinelibrary.wiley.com/doi/10.1002/cbic.202400373
info:eu-repo/semantics/altIdentifier/doi/10.1002/cbic.202400373
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Wiley VCH Verlag
publisher.none.fl_str_mv Wiley VCH Verlag
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 12.993085

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