Utilize este identificador para referenciar este registo: http://hdl.handle.net/10400.21/4945
Título: 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
Autor: Luís, Daniela V.
Silva, Joana
Tomaz, Ana Isabel
Almeida, Rodrigo F. M. de
Larguinho, Miguel
Baptista, Pedro V.
Martins, Luísa Margarida D. R. S.
Silva, Telma F. S.
Borralho, Pedro M.
Rodrigues, Cecília M. P.
Rodrigues, António S.
Pombeiro, Armando J. L.
Fernandes, Alexandra R.
Palavras-chave: Cobalt
1,10-Phenanthroline-5,6-dione
Apoptosis
DNA Cleavage
Human Serum Albumin
Data: Ago-2014
Editora: Springer
Citação: 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
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.
Peer review: yes
URI: http://hdl.handle.net/10400.21/4945
DOI: 10.1007/s00775-014-1110-0
ISSN: 0949-8257
1432-1327
Aparece nas colecções:ISEL - Eng. Quim. Biol. - Artigos

Ficheiros deste registo:
Ficheiro Descrição TamanhoFormato 
Insights into the mechanisms.pdf1,29 MBAdobe PDFVer/Abrir    Acesso Restrito. Solicitar cópia ao autor!


FacebookTwitterDeliciousLinkedInDiggGoogle BookmarksMySpace
Formato BibTex MendeleyEndnote Degois 

Todos os registos no repositório estão protegidos por leis de copyright, com todos os direitos reservados.