Document Detail


Mechanism of Cytotoxicity and Cellular Uptake of Lipophilic Inert Dinuclear Polypyridylruthenium(II) Complexes.
MedLine Citation:
PMID:  21472992     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
The accumulation, uptake mechanism, cytotoxicity, cellular localisation of-and mode of cell death induced by-dinuclear ruthenium(II) complexes ΔΔ/ΛΛ-[{Ru(phen)(2) }(2) {μ-bb(n) }](4+) (Rubb(n) ), where phen is 1,10-phenanthroline, bb(n) is bis[4(4'-methyl-2,2'-bipyridyl)]-1,n-alkane (n=2, 5, 7, 10, 12 or 16), and the corresponding mononuclear complexes containing the bb(n) ligands, were studied in L1210 murine leukaemia cells. Cytotoxicity increased with linker chain length, and the ΔΔ-Rubb(16) complex displayed the highest cytotoxicity of the series, with an IC(50) value of 5 μM, similar to that of carboplatin in the L1210 murine leukaemia cell line. Confocal microscopy and flow cytometry studies indicated that the complexes accumulate in the mitochondria of L1210 cells, with the magnitude of cellular uptake and accumulation increasing with linking chain length in the bb(n) bridge of the metal complex. ΔΔ-Rubb(16) entered the L1210 cells by passive diffusion (with a minor contribution from protein-mediated active transport), inducing cell death via apoptosis. Additionally, metal-complex uptake in leukaemia cells was approximately 16-times that observed in healthy B cells highlighting that the bb(n) series of complexes may have potential as selective anticancer drugs.
Authors:
Michelle J Pisani; Phillip D Fromm; Yanyan Mulyana; Ronald J Clarke; Heinrich Körner; Kirsten Heimann; J Grant Collins; F Richard Keene
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-4-5
Journal Detail:
Title:  ChemMedChem     Volume:  -     ISSN:  1860-7187     ISO Abbreviation:  -     Publication Date:  2011 Apr 
Date Detail:
Created Date:  2011-4-7     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101259013     Medline TA:  ChemMedChem     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Affiliation:
School of Physical, Environmental and Mathematical Sciences, University of New South Wales, Australian Defence Force Academy, Northcott Drive, Canberra, ACT 2600 (Australia), Fax: (+61) 2-6268-8017.
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