The trans-[Ru(PPh3)(2)(N,N-dimethyl-N '-thiophenylthioureato-k(2)O,S)(bipy)] PF6 complex has pro-apoptotic effects on triple negative breast cancer cells and presents low toxicity in vivo
Autor(a) principal: | |
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Data de Publicação: | 2018 |
Outros Autores: | , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1016/j.jinorgbio.2018.05.011 http://hdl.handle.net/11449/164518 |
Resumo: | Triple negative breast cancer (TNBC) is a heterogeneous subtype of breast tumors that does not exhibit the expression of estrogen and progesterone receptors, neither the amplification of the human epidermal growth factor receptor 2 (HER-2) gene. Despite all the advances in cancer treatments, the development of new anticancer drugs for TNBC tumors is still a challenge. There is an increasing interest in new agents to be used in cancer treatment. Ruthenium is a metal that has unique characteristics and important in vivo and in vitro results achieved for cancer treatment. Thus, in this work, with the aim to develop anticancer drugs, three new ruthenium complexes containing acylthiourea ligands have been synthesized and characterized: trans-[Ru (PPh3)(2)(N,N-dibutyl-N'-benzoylthioureato-k(2)O,S)(2,2'-bipyridine (bipy))]PF6 (1), trans-[Ru(PPh3)(2)(N,N-dimethyl-N'-thiophenylthioureato-k(2)O,S)(bipy)PF6 (2) and trans-[Ru(PPh3)(2)(N,N-dimethyl-N'-benzoylthioureatok(2)O,S)(bipy)]PF6 (3). Then, the cytotoxicity of these three new ruthenium complexes was investigated in TNBC MDA-MB-231 and in non-tumor MCF-10A cells. Complex (2) was the most selective complex and was chosen for further studies to verify its effects on cell morphology, adhesion, migration, invasion, induction of apoptosis and DNA damage in vitro, as well as its toxicity and capacity of causing DNA damage in vivo. Complex (2) inhibited proliferation, migration, invasion, adhesion, changed morphology and induced apoptosis, DNA damage and nuclear fragmentation of TNBC cells at lower concentrations compared to non-tumor MCF-10A cells, suggesting an effective action for this complex on tumor cells. Finally, complex (2) did not induce toxicity or caused DNA damage in vivo when low doses were administered to mice. |
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The trans-[Ru(PPh3)(2)(N,N-dimethyl-N '-thiophenylthioureato-k(2)O,S)(bipy)] PF6 complex has pro-apoptotic effects on triple negative breast cancer cells and presents low toxicity in vivoTriple negative breast cancerRuthenium complexesAcylthiourea ligandsIn vivo studiesApoptosisTriple negative breast cancer (TNBC) is a heterogeneous subtype of breast tumors that does not exhibit the expression of estrogen and progesterone receptors, neither the amplification of the human epidermal growth factor receptor 2 (HER-2) gene. Despite all the advances in cancer treatments, the development of new anticancer drugs for TNBC tumors is still a challenge. There is an increasing interest in new agents to be used in cancer treatment. Ruthenium is a metal that has unique characteristics and important in vivo and in vitro results achieved for cancer treatment. Thus, in this work, with the aim to develop anticancer drugs, three new ruthenium complexes containing acylthiourea ligands have been synthesized and characterized: trans-[Ru (PPh3)(2)(N,N-dibutyl-N'-benzoylthioureato-k(2)O,S)(2,2'-bipyridine (bipy))]PF6 (1), trans-[Ru(PPh3)(2)(N,N-dimethyl-N'-thiophenylthioureato-k(2)O,S)(bipy)PF6 (2) and trans-[Ru(PPh3)(2)(N,N-dimethyl-N'-benzoylthioureatok(2)O,S)(bipy)]PF6 (3). Then, the cytotoxicity of these three new ruthenium complexes was investigated in TNBC MDA-MB-231 and in non-tumor MCF-10A cells. Complex (2) was the most selective complex and was chosen for further studies to verify its effects on cell morphology, adhesion, migration, invasion, induction of apoptosis and DNA damage in vitro, as well as its toxicity and capacity of causing DNA damage in vivo. Complex (2) inhibited proliferation, migration, invasion, adhesion, changed morphology and induced apoptosis, DNA damage and nuclear fragmentation of TNBC cells at lower concentrations compared to non-tumor MCF-10A cells, suggesting an effective action for this complex on tumor cells. Finally, complex (2) did not induce toxicity or caused DNA damage in vivo when low doses were administered to mice.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Univ Fed Sao Carlos, Dept Gerontol, Rod Washington Luis,Km 235, BR-13565905 Sao Carlos, SP, BrazilUniv Habana, Fac Quim, Zapata S-N Entre G & Carlitos Aguirre, Havana 10400, CubaUniv Estadual Paulista, Fac Filosofia & Ciencias, Dept Fonoaudiol, Av Hygino Muzzi Filho 737, BR-17525900 Marilia, SP, BrazilUniv Sao Paulo, Inst Fis Sao Carlos, CP 780, BR-13560970 Sao Carlos, SP, BrazilUniv Fed Sao Carlos, Dept Quim, Rod Washington Luis,Km 235, BR-13565905 Sao Carlos, SP, BrazilUniv Estadual Paulista, Fac Filosofia & Ciencias, Dept Fonoaudiol, Av Hygino Muzzi Filho 737, BR-17525900 Marilia, SP, BrazilFAPESP: 2013/00798-2FAPESP: 2015/24940-8FAPESP: 2014/25121-8Elsevier B.V.Universidade Federal de São Carlos (UFSCar)Univ HabanaUniversidade Estadual Paulista (Unesp)Universidade de São Paulo (USP)Becceneri, Amanda BlanquePopolin, Cecilia PatriciaMaria Plutin, AnaMaistro, Edson Luis [UNESP]Castellano, Eduardo ErnestoBatista, Alzir AzevedoCominetti, Marcia Regina2018-11-26T17:54:53Z2018-11-26T17:54:53Z2018-09-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article70-84application/pdfhttp://dx.doi.org/10.1016/j.jinorgbio.2018.05.011Journal Of Inorganic Biochemistry. New York: Elsevier Science Inc, v. 186, p. 70-84, 2018.0162-0134http://hdl.handle.net/11449/16451810.1016/j.jinorgbio.2018.05.011WOS:000441704600010WOS000441704600010.pdf47875216130383150000-0003-0757-7876Web of Sciencereponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengJournal Of Inorganic Biochemistry0,743info:eu-repo/semantics/openAccess2023-11-27T06:15:45Zoai:repositorio.unesp.br:11449/164518Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462023-11-27T06:15:45Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
The trans-[Ru(PPh3)(2)(N,N-dimethyl-N '-thiophenylthioureato-k(2)O,S)(bipy)] PF6 complex has pro-apoptotic effects on triple negative breast cancer cells and presents low toxicity in vivo |
title |
The trans-[Ru(PPh3)(2)(N,N-dimethyl-N '-thiophenylthioureato-k(2)O,S)(bipy)] PF6 complex has pro-apoptotic effects on triple negative breast cancer cells and presents low toxicity in vivo |
spellingShingle |
The trans-[Ru(PPh3)(2)(N,N-dimethyl-N '-thiophenylthioureato-k(2)O,S)(bipy)] PF6 complex has pro-apoptotic effects on triple negative breast cancer cells and presents low toxicity in vivo Becceneri, Amanda Blanque Triple negative breast cancer Ruthenium complexes Acylthiourea ligands In vivo studies Apoptosis |
title_short |
The trans-[Ru(PPh3)(2)(N,N-dimethyl-N '-thiophenylthioureato-k(2)O,S)(bipy)] PF6 complex has pro-apoptotic effects on triple negative breast cancer cells and presents low toxicity in vivo |
title_full |
The trans-[Ru(PPh3)(2)(N,N-dimethyl-N '-thiophenylthioureato-k(2)O,S)(bipy)] PF6 complex has pro-apoptotic effects on triple negative breast cancer cells and presents low toxicity in vivo |
title_fullStr |
The trans-[Ru(PPh3)(2)(N,N-dimethyl-N '-thiophenylthioureato-k(2)O,S)(bipy)] PF6 complex has pro-apoptotic effects on triple negative breast cancer cells and presents low toxicity in vivo |
title_full_unstemmed |
The trans-[Ru(PPh3)(2)(N,N-dimethyl-N '-thiophenylthioureato-k(2)O,S)(bipy)] PF6 complex has pro-apoptotic effects on triple negative breast cancer cells and presents low toxicity in vivo |
title_sort |
The trans-[Ru(PPh3)(2)(N,N-dimethyl-N '-thiophenylthioureato-k(2)O,S)(bipy)] PF6 complex has pro-apoptotic effects on triple negative breast cancer cells and presents low toxicity in vivo |
author |
Becceneri, Amanda Blanque |
author_facet |
Becceneri, Amanda Blanque Popolin, Cecilia Patricia Maria Plutin, Ana Maistro, Edson Luis [UNESP] Castellano, Eduardo Ernesto Batista, Alzir Azevedo Cominetti, Marcia Regina |
author_role |
author |
author2 |
Popolin, Cecilia Patricia Maria Plutin, Ana Maistro, Edson Luis [UNESP] Castellano, Eduardo Ernesto Batista, Alzir Azevedo Cominetti, Marcia Regina |
author2_role |
author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade Federal de São Carlos (UFSCar) Univ Habana Universidade Estadual Paulista (Unesp) Universidade de São Paulo (USP) |
dc.contributor.author.fl_str_mv |
Becceneri, Amanda Blanque Popolin, Cecilia Patricia Maria Plutin, Ana Maistro, Edson Luis [UNESP] Castellano, Eduardo Ernesto Batista, Alzir Azevedo Cominetti, Marcia Regina |
dc.subject.por.fl_str_mv |
Triple negative breast cancer Ruthenium complexes Acylthiourea ligands In vivo studies Apoptosis |
topic |
Triple negative breast cancer Ruthenium complexes Acylthiourea ligands In vivo studies Apoptosis |
description |
Triple negative breast cancer (TNBC) is a heterogeneous subtype of breast tumors that does not exhibit the expression of estrogen and progesterone receptors, neither the amplification of the human epidermal growth factor receptor 2 (HER-2) gene. Despite all the advances in cancer treatments, the development of new anticancer drugs for TNBC tumors is still a challenge. There is an increasing interest in new agents to be used in cancer treatment. Ruthenium is a metal that has unique characteristics and important in vivo and in vitro results achieved for cancer treatment. Thus, in this work, with the aim to develop anticancer drugs, three new ruthenium complexes containing acylthiourea ligands have been synthesized and characterized: trans-[Ru (PPh3)(2)(N,N-dibutyl-N'-benzoylthioureato-k(2)O,S)(2,2'-bipyridine (bipy))]PF6 (1), trans-[Ru(PPh3)(2)(N,N-dimethyl-N'-thiophenylthioureato-k(2)O,S)(bipy)PF6 (2) and trans-[Ru(PPh3)(2)(N,N-dimethyl-N'-benzoylthioureatok(2)O,S)(bipy)]PF6 (3). Then, the cytotoxicity of these three new ruthenium complexes was investigated in TNBC MDA-MB-231 and in non-tumor MCF-10A cells. Complex (2) was the most selective complex and was chosen for further studies to verify its effects on cell morphology, adhesion, migration, invasion, induction of apoptosis and DNA damage in vitro, as well as its toxicity and capacity of causing DNA damage in vivo. Complex (2) inhibited proliferation, migration, invasion, adhesion, changed morphology and induced apoptosis, DNA damage and nuclear fragmentation of TNBC cells at lower concentrations compared to non-tumor MCF-10A cells, suggesting an effective action for this complex on tumor cells. Finally, complex (2) did not induce toxicity or caused DNA damage in vivo when low doses were administered to mice. |
publishDate |
2018 |
dc.date.none.fl_str_mv |
2018-11-26T17:54:53Z 2018-11-26T17:54:53Z 2018-09-01 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://dx.doi.org/10.1016/j.jinorgbio.2018.05.011 Journal Of Inorganic Biochemistry. New York: Elsevier Science Inc, v. 186, p. 70-84, 2018. 0162-0134 http://hdl.handle.net/11449/164518 10.1016/j.jinorgbio.2018.05.011 WOS:000441704600010 WOS000441704600010.pdf 4787521613038315 0000-0003-0757-7876 |
url |
http://dx.doi.org/10.1016/j.jinorgbio.2018.05.011 http://hdl.handle.net/11449/164518 |
identifier_str_mv |
Journal Of Inorganic Biochemistry. New York: Elsevier Science Inc, v. 186, p. 70-84, 2018. 0162-0134 10.1016/j.jinorgbio.2018.05.011 WOS:000441704600010 WOS000441704600010.pdf 4787521613038315 0000-0003-0757-7876 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Journal Of Inorganic Biochemistry 0,743 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
70-84 application/pdf |
dc.publisher.none.fl_str_mv |
Elsevier B.V. |
publisher.none.fl_str_mv |
Elsevier B.V. |
dc.source.none.fl_str_mv |
Web of Science reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
|
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1799965090214051840 |