Anti-metastatic action of an N4-aryl substituted thiosemicarbazone on advanced triple negative breast cancer

Autores
Sólimo, Aldana María; Soraires Santacruz, Maria Cristina; Vanzulli, Silvia; Coggiola, Osvaldo; Bal, Elisa Dora; Finkielsztein, Liliana Mónica; Callero, Mariana Alejandra
Año de publicación
2020
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Purpose: Advanced triple negative breast cancer (ATNBC) is defined by a lack of expression of hormones receptors as well as HER2/neu and its high probability of visceral metastasis. This pathology is associated with a poor prognosis. Previously, we found that T2, an N4 -arylsubstituted thiosemicarbazone (N4 -TSC), had cytotoxic effect on human breast cancer cells lines. Hence, in this study, we investigated the anti-metastasic action of T2 on ATNBC. Methods: In order to deepen T2 action mode on ATNBC, we first confirmed T2 cytotoxicity on a panel of TNBC cells and then continued studying T2 effects in vitro an in vivo on the syngeneic 4T1 mouse model. Results: We found that T2 had a cytotoxic effect comparable to chemotherapeutics used in present treatment schemes for ATNBC. T2 treatment not only induced apoptosis, but it also down-modulated 4T1 invasive and metastatic-associated capacities, such as clonogenicity, migration and metallo-proteases activity. Moreover, this agent reduced the number of 4T1 cancer stem cells. Finally, T2 treatment induced a more differentiated cell phenotype and the overexpression of the metastasis suppressor gene NDRG-1. In vivo assays showed that T2 reduced tumor burden, down modulated local tumor invasion and significantly reduced the number of lung metastases in the 4T1 advanced TNBC murine model, while the compound did not exhibit intolerable toxicity. Conclusion: This study provided evidence that T2 not only exerted an anti-tumor activity but it also showed antiinvasive and anti-metastatic actions on ATNBC in vivo and in vitro, suggesting that T2 could be considered as a promising therapy that deserves further analysis.
Fil: Sólimo, Aldana María. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina
Fil: Soraires Santacruz, Maria Cristina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Química Medicinal; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; Argentina
Fil: Vanzulli, Silvia. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; Argentina
Fil: Coggiola, Osvaldo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina
Fil: Bal, Elisa Dora. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Finkielsztein, Liliana Mónica. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Química Medicinal; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; Argentina
Fil: Callero, Mariana Alejandra. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Materia
BIOCHEMISTRY
CANCER RESEARCH
CELL BIOLOGY
INVASION
METASTASIS
MOLECULAR BIOLOGY
ONCOLOGY
STEM CELLS
THIOSEMICARBAZONES
TRIPLE NEGATIVE BREAST CANCER
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/146634
Acceder
id CONICETDig_a614a24098c7484445029b7e3c06043c
oai_identifier_str oai:ri.conicet.gov.ar:11336/146634
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Anti-metastatic action of an N4-aryl substituted thiosemicarbazone on advanced triple negative breast cancerSólimo, Aldana MaríaSoraires Santacruz, Maria CristinaVanzulli, SilviaCoggiola, OsvaldoBal, Elisa DoraFinkielsztein, Liliana MónicaCallero, Mariana AlejandraBIOCHEMISTRYCANCER RESEARCHCELL BIOLOGYINVASIONMETASTASISMOLECULAR BIOLOGYONCOLOGYSTEM CELLSTHIOSEMICARBAZONESTRIPLE NEGATIVE BREAST CANCERhttps://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3Purpose: Advanced triple negative breast cancer (ATNBC) is defined by a lack of expression of hormones receptors as well as HER2/neu and its high probability of visceral metastasis. This pathology is associated with a poor prognosis. Previously, we found that T2, an N4 -arylsubstituted thiosemicarbazone (N4 -TSC), had cytotoxic effect on human breast cancer cells lines. Hence, in this study, we investigated the anti-metastasic action of T2 on ATNBC. Methods: In order to deepen T2 action mode on ATNBC, we first confirmed T2 cytotoxicity on a panel of TNBC cells and then continued studying T2 effects in vitro an in vivo on the syngeneic 4T1 mouse model. Results: We found that T2 had a cytotoxic effect comparable to chemotherapeutics used in present treatment schemes for ATNBC. T2 treatment not only induced apoptosis, but it also down-modulated 4T1 invasive and metastatic-associated capacities, such as clonogenicity, migration and metallo-proteases activity. Moreover, this agent reduced the number of 4T1 cancer stem cells. Finally, T2 treatment induced a more differentiated cell phenotype and the overexpression of the metastasis suppressor gene NDRG-1. In vivo assays showed that T2 reduced tumor burden, down modulated local tumor invasion and significantly reduced the number of lung metastases in the 4T1 advanced TNBC murine model, while the compound did not exhibit intolerable toxicity. Conclusion: This study provided evidence that T2 not only exerted an anti-tumor activity but it also showed antiinvasive and anti-metastatic actions on ATNBC in vivo and in vitro, suggesting that T2 could be considered as a promising therapy that deserves further analysis.Fil: Sólimo, Aldana María. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; ArgentinaFil: Soraires Santacruz, Maria Cristina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Química Medicinal; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; ArgentinaFil: Vanzulli, Silvia. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; ArgentinaFil: Coggiola, Osvaldo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; ArgentinaFil: Bal, Elisa Dora. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Finkielsztein, Liliana Mónica. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Química Medicinal; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; ArgentinaFil: Callero, Mariana Alejandra. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaElsevier2020-10info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/146634Sólimo, Aldana María; Soraires Santacruz, Maria Cristina; Vanzulli, Silvia; Coggiola, Osvaldo; Bal, Elisa Dora; et al.; Anti-metastatic action of an N4-aryl substituted thiosemicarbazone on advanced triple negative breast cancer; Elsevier; Heliyon; 6; 10; 10-2020; 1-112405-8440CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.cell.com/heliyon/fulltext/S2405-8440(20)32004-1?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS2405844020320041%3Fshowall%3Dtrueinfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.heliyon.2020.e05161info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:49:21Zoai:ri.conicet.gov.ar:11336/146634instacron: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:34982025-09-03 09:49:22.18CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Anti-metastatic action of an N4-aryl substituted thiosemicarbazone on advanced triple negative breast cancer
title Anti-metastatic action of an N4-aryl substituted thiosemicarbazone on advanced triple negative breast cancer
spellingShingle Anti-metastatic action of an N4-aryl substituted thiosemicarbazone on advanced triple negative breast cancer
Sólimo, Aldana María
BIOCHEMISTRY
CANCER RESEARCH
CELL BIOLOGY
INVASION
METASTASIS
MOLECULAR BIOLOGY
ONCOLOGY
STEM CELLS
THIOSEMICARBAZONES
TRIPLE NEGATIVE BREAST CANCER
title_short Anti-metastatic action of an N4-aryl substituted thiosemicarbazone on advanced triple negative breast cancer
title_full Anti-metastatic action of an N4-aryl substituted thiosemicarbazone on advanced triple negative breast cancer
title_fullStr Anti-metastatic action of an N4-aryl substituted thiosemicarbazone on advanced triple negative breast cancer
title_full_unstemmed Anti-metastatic action of an N4-aryl substituted thiosemicarbazone on advanced triple negative breast cancer
title_sort Anti-metastatic action of an N4-aryl substituted thiosemicarbazone on advanced triple negative breast cancer
dc.creator.none.fl_str_mv Sólimo, Aldana María
Soraires Santacruz, Maria Cristina
Vanzulli, Silvia
Coggiola, Osvaldo
Bal, Elisa Dora
Finkielsztein, Liliana Mónica
Callero, Mariana Alejandra
author Sólimo, Aldana María
author_facet Sólimo, Aldana María
Soraires Santacruz, Maria Cristina
Vanzulli, Silvia
Coggiola, Osvaldo
Bal, Elisa Dora
Finkielsztein, Liliana Mónica
Callero, Mariana Alejandra
author_role author
author2 Soraires Santacruz, Maria Cristina
Vanzulli, Silvia
Coggiola, Osvaldo
Bal, Elisa Dora
Finkielsztein, Liliana Mónica
Callero, Mariana Alejandra
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv BIOCHEMISTRY
CANCER RESEARCH
CELL BIOLOGY
INVASION
METASTASIS
MOLECULAR BIOLOGY
ONCOLOGY
STEM CELLS
THIOSEMICARBAZONES
TRIPLE NEGATIVE BREAST CANCER
topic BIOCHEMISTRY
CANCER RESEARCH
CELL BIOLOGY
INVASION
METASTASIS
MOLECULAR BIOLOGY
ONCOLOGY
STEM CELLS
THIOSEMICARBAZONES
TRIPLE NEGATIVE BREAST CANCER
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Purpose: Advanced triple negative breast cancer (ATNBC) is defined by a lack of expression of hormones receptors as well as HER2/neu and its high probability of visceral metastasis. This pathology is associated with a poor prognosis. Previously, we found that T2, an N4 -arylsubstituted thiosemicarbazone (N4 -TSC), had cytotoxic effect on human breast cancer cells lines. Hence, in this study, we investigated the anti-metastasic action of T2 on ATNBC. Methods: In order to deepen T2 action mode on ATNBC, we first confirmed T2 cytotoxicity on a panel of TNBC cells and then continued studying T2 effects in vitro an in vivo on the syngeneic 4T1 mouse model. Results: We found that T2 had a cytotoxic effect comparable to chemotherapeutics used in present treatment schemes for ATNBC. T2 treatment not only induced apoptosis, but it also down-modulated 4T1 invasive and metastatic-associated capacities, such as clonogenicity, migration and metallo-proteases activity. Moreover, this agent reduced the number of 4T1 cancer stem cells. Finally, T2 treatment induced a more differentiated cell phenotype and the overexpression of the metastasis suppressor gene NDRG-1. In vivo assays showed that T2 reduced tumor burden, down modulated local tumor invasion and significantly reduced the number of lung metastases in the 4T1 advanced TNBC murine model, while the compound did not exhibit intolerable toxicity. Conclusion: This study provided evidence that T2 not only exerted an anti-tumor activity but it also showed antiinvasive and anti-metastatic actions on ATNBC in vivo and in vitro, suggesting that T2 could be considered as a promising therapy that deserves further analysis.
Fil: Sólimo, Aldana María. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina
Fil: Soraires Santacruz, Maria Cristina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Química Medicinal; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; Argentina
Fil: Vanzulli, Silvia. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; Argentina
Fil: Coggiola, Osvaldo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina
Fil: Bal, Elisa Dora. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Finkielsztein, Liliana Mónica. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Química Medicinal; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; Argentina
Fil: Callero, Mariana Alejandra. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
description Purpose: Advanced triple negative breast cancer (ATNBC) is defined by a lack of expression of hormones receptors as well as HER2/neu and its high probability of visceral metastasis. This pathology is associated with a poor prognosis. Previously, we found that T2, an N4 -arylsubstituted thiosemicarbazone (N4 -TSC), had cytotoxic effect on human breast cancer cells lines. Hence, in this study, we investigated the anti-metastasic action of T2 on ATNBC. Methods: In order to deepen T2 action mode on ATNBC, we first confirmed T2 cytotoxicity on a panel of TNBC cells and then continued studying T2 effects in vitro an in vivo on the syngeneic 4T1 mouse model. Results: We found that T2 had a cytotoxic effect comparable to chemotherapeutics used in present treatment schemes for ATNBC. T2 treatment not only induced apoptosis, but it also down-modulated 4T1 invasive and metastatic-associated capacities, such as clonogenicity, migration and metallo-proteases activity. Moreover, this agent reduced the number of 4T1 cancer stem cells. Finally, T2 treatment induced a more differentiated cell phenotype and the overexpression of the metastasis suppressor gene NDRG-1. In vivo assays showed that T2 reduced tumor burden, down modulated local tumor invasion and significantly reduced the number of lung metastases in the 4T1 advanced TNBC murine model, while the compound did not exhibit intolerable toxicity. Conclusion: This study provided evidence that T2 not only exerted an anti-tumor activity but it also showed antiinvasive and anti-metastatic actions on ATNBC in vivo and in vitro, suggesting that T2 could be considered as a promising therapy that deserves further analysis.
publishDate 2020
dc.date.none.fl_str_mv 2020-10
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/11336/146634
Sólimo, Aldana María; Soraires Santacruz, Maria Cristina; Vanzulli, Silvia; Coggiola, Osvaldo; Bal, Elisa Dora; et al.; Anti-metastatic action of an N4-aryl substituted thiosemicarbazone on advanced triple negative breast cancer; Elsevier; Heliyon; 6; 10; 10-2020; 1-11
2405-8440
CONICET Digital
CONICET
url http://hdl.handle.net/11336/146634
identifier_str_mv Sólimo, Aldana María; Soraires Santacruz, Maria Cristina; Vanzulli, Silvia; Coggiola, Osvaldo; Bal, Elisa Dora; et al.; Anti-metastatic action of an N4-aryl substituted thiosemicarbazone on advanced triple negative breast cancer; Elsevier; Heliyon; 6; 10; 10-2020; 1-11
2405-8440
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://www.cell.com/heliyon/fulltext/S2405-8440(20)32004-1?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS2405844020320041%3Fshowall%3Dtrue
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.heliyon.2020.e05161
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
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reponame_str CONICET Digital (CONICET)
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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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