Insights into the mechanims underlyng the antiproliferative potential of a Co(II) coordination compound bearing 1,10-Phenanthroline-5,6-Dione: DNA and protein interaction studies

Detalhes bibliográficos
Autor(a) principal: Luís, Daniela V.
Data de Publicação: 2014
Outros Autores: Silva, Joana, Tomaz, Ana Isabel, Almeida, Rodrigo F. M. de, Larguinho, Miguel, Baptista, Pedro V., Martins, Luisa, Silva, Telma F. S., Borralho, Pedro M., Rodrigues, Cecília M. P., Rodrigues, António S., Pombeiro, Armando, Fernandes, Alexandra R.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10400.21/4945
Resumo: The very high antiproliferative activity of [Co(Cl)(H2O)(phendione)(2)][BF4] (phendione is 1,10-phenanthroline-5,6-dione) against three human tumor cell lines (half-maximal inhibitory concentration below 1 mu M) and its slight selectivity for the colorectal tumor cell line compared with healthy human fibroblasts led us to explore the mechanisms of action underlying this promising antitumor potential. As previously shown by our group, this complex induces cell cycle arrest in S phase and subsequent cell death by apoptosis and it also reduces the expression of proteins typically upregulated in tumors. In the present work, we demonstrate that [Co(Cl)(phendione)(2)(H2O)][BF4] (1) does not reduce the viability of nontumorigenic breast epithelial cells by more than 85 % at 1 mu M, (2) promotes the upregulation of proapoptotic Bax and cell-cycle-related p21, and (3) induces release of lactate dehydrogenase, which is partially reversed by ursodeoxycholic acid. DNA interaction studies were performed to uncover the genotoxicity of the complex and demonstrate that even though it displays K (b) (+/- A standard error of the mean) of (3.48 +/- A 0.03) x 10(5) M-1 and is able to produce double-strand breaks in a concentration-dependent manner, it does not exert any clastogenic effect ex vivo, ruling out DNA as a major cellular target for the complex. Steady-state and time-resolved fluorescence spectroscopy studies are indicative of a strong and specific interaction of the complex with human serum albumin, involving one binding site, at a distance of approximately 1.5 nm for the Trp214 indole side chain with log K (b) similar to 4.7, thus suggesting that this complex can be efficiently transported by albumin in the blood plasma.
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spelling Insights into the mechanims underlyng the antiproliferative potential of a Co(II) coordination compound bearing 1,10-Phenanthroline-5,6-Dione: DNA and protein interaction studiesCobalt1,10-Phenanthroline-5,6-dioneApoptosisDNA CleavageHuman Serum AlbuminThe very high antiproliferative activity of [Co(Cl)(H2O)(phendione)(2)][BF4] (phendione is 1,10-phenanthroline-5,6-dione) against three human tumor cell lines (half-maximal inhibitory concentration below 1 mu M) and its slight selectivity for the colorectal tumor cell line compared with healthy human fibroblasts led us to explore the mechanisms of action underlying this promising antitumor potential. As previously shown by our group, this complex induces cell cycle arrest in S phase and subsequent cell death by apoptosis and it also reduces the expression of proteins typically upregulated in tumors. In the present work, we demonstrate that [Co(Cl)(phendione)(2)(H2O)][BF4] (1) does not reduce the viability of nontumorigenic breast epithelial cells by more than 85 % at 1 mu M, (2) promotes the upregulation of proapoptotic Bax and cell-cycle-related p21, and (3) induces release of lactate dehydrogenase, which is partially reversed by ursodeoxycholic acid. DNA interaction studies were performed to uncover the genotoxicity of the complex and demonstrate that even though it displays K (b) (+/- A standard error of the mean) of (3.48 +/- A 0.03) x 10(5) M-1 and is able to produce double-strand breaks in a concentration-dependent manner, it does not exert any clastogenic effect ex vivo, ruling out DNA as a major cellular target for the complex. Steady-state and time-resolved fluorescence spectroscopy studies are indicative of a strong and specific interaction of the complex with human serum albumin, involving one binding site, at a distance of approximately 1.5 nm for the Trp214 indole side chain with log K (b) similar to 4.7, thus suggesting that this complex can be efficiently transported by albumin in the blood plasma.SpringerRCIPLLuís, Daniela V.Silva, JoanaTomaz, Ana IsabelAlmeida, Rodrigo F. M. deLarguinho, MiguelBaptista, Pedro V.Martins, LuisaSilva, Telma F. S.Borralho, Pedro M.Rodrigues, Cecília M. P.Rodrigues, António S.Pombeiro, ArmandoFernandes, Alexandra R.2015-08-24T11:38:40Z2014-082014-08-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.21/4945engLUÍS, Daniel V.; [et al] – Insights into the mechanims underlyng the antiproliferative potential of a Co(II) coordination compound bearing 1,10-Phenanthroline-5,6-Dione: DNA and protein interaction studies. Journal of Biological Inorganic Chemistry. ISSN: 0949-8257. Vol. 19, nr. 6 (2014), pp. 787-8030949-825710.1007/s00775-014-1110-0metadata 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:RCAAP2023-08-03T09:47:41Zoai:repositorio.ipl.pt:10400.21/4945Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T20:14:18.216492Repositório 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 Insights into the mechanims underlyng the antiproliferative potential of a Co(II) coordination compound bearing 1,10-Phenanthroline-5,6-Dione: DNA and protein interaction studies
title Insights into the mechanims underlyng the antiproliferative potential of a Co(II) coordination compound bearing 1,10-Phenanthroline-5,6-Dione: DNA and protein interaction studies
spellingShingle Insights into the mechanims underlyng the antiproliferative potential of a Co(II) coordination compound bearing 1,10-Phenanthroline-5,6-Dione: DNA and protein interaction studies
Luís, Daniela V.
Cobalt
1,10-Phenanthroline-5,6-dione
Apoptosis
DNA Cleavage
Human Serum Albumin
title_short Insights into the mechanims underlyng the antiproliferative potential of a Co(II) coordination compound bearing 1,10-Phenanthroline-5,6-Dione: DNA and protein interaction studies
title_full Insights into the mechanims underlyng the antiproliferative potential of a Co(II) coordination compound bearing 1,10-Phenanthroline-5,6-Dione: DNA and protein interaction studies
title_fullStr Insights into the mechanims underlyng the antiproliferative potential of a Co(II) coordination compound bearing 1,10-Phenanthroline-5,6-Dione: DNA and protein interaction studies
title_full_unstemmed Insights into the mechanims underlyng the antiproliferative potential of a Co(II) coordination compound bearing 1,10-Phenanthroline-5,6-Dione: DNA and protein interaction studies
title_sort Insights into the mechanims underlyng the antiproliferative potential of a Co(II) coordination compound bearing 1,10-Phenanthroline-5,6-Dione: DNA and protein interaction studies
author Luís, Daniela V.
author_facet Luís, Daniela V.
Silva, Joana
Tomaz, Ana Isabel
Almeida, Rodrigo F. M. de
Larguinho, Miguel
Baptista, Pedro V.
Martins, Luisa
Silva, Telma F. S.
Borralho, Pedro M.
Rodrigues, Cecília M. P.
Rodrigues, António S.
Pombeiro, Armando
Fernandes, Alexandra R.
author_role author
author2 Silva, Joana
Tomaz, Ana Isabel
Almeida, Rodrigo F. M. de
Larguinho, Miguel
Baptista, Pedro V.
Martins, Luisa
Silva, Telma F. S.
Borralho, Pedro M.
Rodrigues, Cecília M. P.
Rodrigues, António S.
Pombeiro, Armando
Fernandes, Alexandra R.
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv RCIPL
dc.contributor.author.fl_str_mv Luís, Daniela V.
Silva, Joana
Tomaz, Ana Isabel
Almeida, Rodrigo F. M. de
Larguinho, Miguel
Baptista, Pedro V.
Martins, Luisa
Silva, Telma F. S.
Borralho, Pedro M.
Rodrigues, Cecília M. P.
Rodrigues, António S.
Pombeiro, Armando
Fernandes, Alexandra R.
dc.subject.por.fl_str_mv Cobalt
1,10-Phenanthroline-5,6-dione
Apoptosis
DNA Cleavage
Human Serum Albumin
topic Cobalt
1,10-Phenanthroline-5,6-dione
Apoptosis
DNA Cleavage
Human Serum Albumin
description The very high antiproliferative activity of [Co(Cl)(H2O)(phendione)(2)][BF4] (phendione is 1,10-phenanthroline-5,6-dione) against three human tumor cell lines (half-maximal inhibitory concentration below 1 mu M) and its slight selectivity for the colorectal tumor cell line compared with healthy human fibroblasts led us to explore the mechanisms of action underlying this promising antitumor potential. As previously shown by our group, this complex induces cell cycle arrest in S phase and subsequent cell death by apoptosis and it also reduces the expression of proteins typically upregulated in tumors. In the present work, we demonstrate that [Co(Cl)(phendione)(2)(H2O)][BF4] (1) does not reduce the viability of nontumorigenic breast epithelial cells by more than 85 % at 1 mu M, (2) promotes the upregulation of proapoptotic Bax and cell-cycle-related p21, and (3) induces release of lactate dehydrogenase, which is partially reversed by ursodeoxycholic acid. DNA interaction studies were performed to uncover the genotoxicity of the complex and demonstrate that even though it displays K (b) (+/- A standard error of the mean) of (3.48 +/- A 0.03) x 10(5) M-1 and is able to produce double-strand breaks in a concentration-dependent manner, it does not exert any clastogenic effect ex vivo, ruling out DNA as a major cellular target for the complex. Steady-state and time-resolved fluorescence spectroscopy studies are indicative of a strong and specific interaction of the complex with human serum albumin, involving one binding site, at a distance of approximately 1.5 nm for the Trp214 indole side chain with log K (b) similar to 4.7, thus suggesting that this complex can be efficiently transported by albumin in the blood plasma.
publishDate 2014
dc.date.none.fl_str_mv 2014-08
2014-08-01T00:00:00Z
2015-08-24T11:38:40Z
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/10400.21/4945
url http://hdl.handle.net/10400.21/4945
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv LUÍS, Daniel V.; [et al] – Insights into the mechanims underlyng the antiproliferative potential of a Co(II) coordination compound bearing 1,10-Phenanthroline-5,6-Dione: DNA and protein interaction studies. Journal of Biological Inorganic Chemistry. ISSN: 0949-8257. Vol. 19, nr. 6 (2014), pp. 787-803
0949-8257
10.1007/s00775-014-1110-0
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publisher.none.fl_str_mv Springer
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