New water-soluble Ruthenium(II) cytotoxic complex: biological activity and celular distribution
Autor(a) principal: | |
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Data de Publicação: | 2014 |
Outros Autores: | , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10400.21/4953 |
Resumo: | A novel water soluble organometallic compound, [RuCp(mTPPMSNa)(2,2'-bipy)][CF3SO3] (TM85, where Cp=eta(5)-cyclopentadienyl, mTPPMS = diphenylphosphane-benzene-3-sulfonate and 2,2'-bipy = 2,2'-bipyridine) is presented herein. Studies of interactions with relevant proteins were performed to understand the behavior and mode of action of this complex in the biological environment. Electrochemical and fluorescence studies showed that TM85 strongly binds to albumin. Studies carried out to study the formation of TM85 which adducts with ubiquitin and cytochrome c were performed by electrospray ionization mass spectrometry (ESI-MS). Antitumor activity was evaluated against a variety of human cancer cell lines, namely A2780, A2780cisR, MCF7, MDAMB231, HT29, PC3 and V79 non-tumorigenic cells and compared with the reference drug cisplatin. TM85 cytotoxic effect was reduced in the presence of endocytosis modulators at low temperatures, suggesting an energy-dependent mechanism consistent with endocytosis. Ultrastructural analysis by transmission electron microscopy (TEM) revealed that TM85 targets the endomembranar system disrupting the Golgi and also affects the mitochondria. Disruption of plasma membrane observed by flow cytometry could lead to cellular damage and cell death. On the whole, the biological activity evaluated herein combined with the water solubility property suggests that complex TM85 could be a promising anticancer agent. (C) 2013 Elsevier Inc. All rights reserved. |
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New water-soluble Ruthenium(II) cytotoxic complex: biological activity and celular distributionRutheniumCyclopentadienylCytotoxicityCellular UptakeAlbuminUbiquitinA novel water soluble organometallic compound, [RuCp(mTPPMSNa)(2,2'-bipy)][CF3SO3] (TM85, where Cp=eta(5)-cyclopentadienyl, mTPPMS = diphenylphosphane-benzene-3-sulfonate and 2,2'-bipy = 2,2'-bipyridine) is presented herein. Studies of interactions with relevant proteins were performed to understand the behavior and mode of action of this complex in the biological environment. Electrochemical and fluorescence studies showed that TM85 strongly binds to albumin. Studies carried out to study the formation of TM85 which adducts with ubiquitin and cytochrome c were performed by electrospray ionization mass spectrometry (ESI-MS). Antitumor activity was evaluated against a variety of human cancer cell lines, namely A2780, A2780cisR, MCF7, MDAMB231, HT29, PC3 and V79 non-tumorigenic cells and compared with the reference drug cisplatin. TM85 cytotoxic effect was reduced in the presence of endocytosis modulators at low temperatures, suggesting an energy-dependent mechanism consistent with endocytosis. Ultrastructural analysis by transmission electron microscopy (TEM) revealed that TM85 targets the endomembranar system disrupting the Golgi and also affects the mitochondria. Disruption of plasma membrane observed by flow cytometry could lead to cellular damage and cell death. On the whole, the biological activity evaluated herein combined with the water solubility property suggests that complex TM85 could be a promising anticancer agent. (C) 2013 Elsevier Inc. All rights reserved.Elsevier Science IncRCIPLMorais, Tânia S.Santos, Filipa C.Jorge, Tiago F.Côrte-Real, LeonorMadeira, Paulo J. AmorimMarques, FernandaRobalo, Maria PaulaMatos, AntónioSantos, IsabelGarcia, M. Helena2015-08-24T13:34:46Z2014-012014-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.21/4953engMORAIS, Tânia S.; [et al] – New water-soluble Ruthenium(II) Cytotoxic Complex: biological activity and celular distribution. Journal of Inorganic Biochemistry. ISSN: 0162-0134. Vol. 130 (2014), pp. 1-140162-013410.1016/j.jinorgbio.2013.09.013metadata only accessinfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-08-03T09:47:43Zoai:repositorio.ipl.pt:10400.21/4953Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T20:14:18.662716Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
New water-soluble Ruthenium(II) cytotoxic complex: biological activity and celular distribution |
title |
New water-soluble Ruthenium(II) cytotoxic complex: biological activity and celular distribution |
spellingShingle |
New water-soluble Ruthenium(II) cytotoxic complex: biological activity and celular distribution Morais, Tânia S. Ruthenium Cyclopentadienyl Cytotoxicity Cellular Uptake Albumin Ubiquitin |
title_short |
New water-soluble Ruthenium(II) cytotoxic complex: biological activity and celular distribution |
title_full |
New water-soluble Ruthenium(II) cytotoxic complex: biological activity and celular distribution |
title_fullStr |
New water-soluble Ruthenium(II) cytotoxic complex: biological activity and celular distribution |
title_full_unstemmed |
New water-soluble Ruthenium(II) cytotoxic complex: biological activity and celular distribution |
title_sort |
New water-soluble Ruthenium(II) cytotoxic complex: biological activity and celular distribution |
author |
Morais, Tânia S. |
author_facet |
Morais, Tânia S. Santos, Filipa C. Jorge, Tiago F. Côrte-Real, Leonor Madeira, Paulo J. Amorim Marques, Fernanda Robalo, Maria Paula Matos, António Santos, Isabel Garcia, M. Helena |
author_role |
author |
author2 |
Santos, Filipa C. Jorge, Tiago F. Côrte-Real, Leonor Madeira, Paulo J. Amorim Marques, Fernanda Robalo, Maria Paula Matos, António Santos, Isabel Garcia, M. Helena |
author2_role |
author author author author author author author author author |
dc.contributor.none.fl_str_mv |
RCIPL |
dc.contributor.author.fl_str_mv |
Morais, Tânia S. Santos, Filipa C. Jorge, Tiago F. Côrte-Real, Leonor Madeira, Paulo J. Amorim Marques, Fernanda Robalo, Maria Paula Matos, António Santos, Isabel Garcia, M. Helena |
dc.subject.por.fl_str_mv |
Ruthenium Cyclopentadienyl Cytotoxicity Cellular Uptake Albumin Ubiquitin |
topic |
Ruthenium Cyclopentadienyl Cytotoxicity Cellular Uptake Albumin Ubiquitin |
description |
A novel water soluble organometallic compound, [RuCp(mTPPMSNa)(2,2'-bipy)][CF3SO3] (TM85, where Cp=eta(5)-cyclopentadienyl, mTPPMS = diphenylphosphane-benzene-3-sulfonate and 2,2'-bipy = 2,2'-bipyridine) is presented herein. Studies of interactions with relevant proteins were performed to understand the behavior and mode of action of this complex in the biological environment. Electrochemical and fluorescence studies showed that TM85 strongly binds to albumin. Studies carried out to study the formation of TM85 which adducts with ubiquitin and cytochrome c were performed by electrospray ionization mass spectrometry (ESI-MS). Antitumor activity was evaluated against a variety of human cancer cell lines, namely A2780, A2780cisR, MCF7, MDAMB231, HT29, PC3 and V79 non-tumorigenic cells and compared with the reference drug cisplatin. TM85 cytotoxic effect was reduced in the presence of endocytosis modulators at low temperatures, suggesting an energy-dependent mechanism consistent with endocytosis. Ultrastructural analysis by transmission electron microscopy (TEM) revealed that TM85 targets the endomembranar system disrupting the Golgi and also affects the mitochondria. Disruption of plasma membrane observed by flow cytometry could lead to cellular damage and cell death. On the whole, the biological activity evaluated herein combined with the water solubility property suggests that complex TM85 could be a promising anticancer agent. (C) 2013 Elsevier Inc. All rights reserved. |
publishDate |
2014 |
dc.date.none.fl_str_mv |
2014-01 2014-01-01T00:00:00Z 2015-08-24T13:34:46Z |
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://hdl.handle.net/10400.21/4953 |
url |
http://hdl.handle.net/10400.21/4953 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
MORAIS, Tânia S.; [et al] – New water-soluble Ruthenium(II) Cytotoxic Complex: biological activity and celular distribution. Journal of Inorganic Biochemistry. ISSN: 0162-0134. Vol. 130 (2014), pp. 1-14 0162-0134 10.1016/j.jinorgbio.2013.09.013 |
dc.rights.driver.fl_str_mv |
metadata only access info:eu-repo/semantics/openAccess |
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metadata only access |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Elsevier Science Inc |
publisher.none.fl_str_mv |
Elsevier Science Inc |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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