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Contrasting cellular uptake pathways for chlorido and iodido iminopyridine ruthenium arene anticancer complexes.
MedLine Citation:
PMID:  23138378     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
The pathways involved in cellular uptake and accumulation of iminopyridine complexes of general formula [Ru(η(6)-p-cymene)(N,N-dimethyl-N'-[(E)-pyridine-2-ylmethylidene]benzene-1,4-diamine)X]PF(6) bearing two different halido ligands X = Cl or I, have been explored. The ratio of passive/active cellular accumulation of Ru in A2780 human ovarian cancer cells is compared and contrasted with cisplatin. Also, saturation of cellular uptake, time-dependence of cellular influx/efflux equilibria, together with endocytotic pathways such as caveolae and facilitated diffusion are investigated and discussed. Temperature dependence studies of Ru accumulation in the A2780 cells show that in contrast to cisplatin (CDDP) and chlorido complex , which are taken up largely through active transport, the iodido complex enters cells via passive transport. The cellular efflux of Ru is slow (ca. 25% retained after 72 h) and is partially inhibited by verapamil, implicating the P-gp protein in the efflux mechanism. Ouabain inhibition experiments suggest that the cellular uptake of these ruthenium complexes relies at least in part on facilitated diffusion, and in particular is dependent on the membrane potential. In addition the finding that depletion of cellular ATP with antimycin A had little effect on cellular Ru accumulation from iodido complex is consistent with passive diffusion. In contrast, ATP depletion caused a major increase in cellular accumulation of ruthenium from chlorido complex .
Authors:
Isolda Romero-Canelón; Ana M Pizarro; Abraha Habtemariam; Peter J Sadler
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-11-9
Journal Detail:
Title:  Metallomics : integrated biometal science     Volume:  -     ISSN:  1756-591X     ISO Abbreviation:  Metallomics     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-11-9     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101478346     Medline TA:  Metallomics     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Department of Chemistry, University of Warwick, Coventry CV4 7AL, UK. p.j.sadler@warwick.ac.uk.
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