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Mechanism of Cytotoxicity and Cellular Uptake of Lipophilic Inert Dinuclear Polypyridylruthenium(II) Complexes
Citation
Pisani, MJ and Fromm, PD and Mulyana, Y and Clarke, RJ and Korner, H and Heimann, K and Collins, JG and Keene, FR, Mechanism of Cytotoxicity and Cellular Uptake of Lipophilic Inert Dinuclear Polypyridylruthenium(II) Complexes, ChemMedChem: chemistry enabling drug discovery, 6, (5) pp. 848-858. ISSN 1860-7179 (2011) [Refereed Article]
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Copyright Statement
Copyright © 2011 The definitive published version is available online at: http://onlinelibrary.wiley.com/
DOI: doi:10.1002/cmdc.201100053
Abstract
The accumulation, uptake mechanism, cytotoxicity, cellular localisation
of—and mode of cell death induced by—dinuclear
ruthenium(II) complexes DD/LL-[{Ru(phen)2}2{m-bbn}]4+ (Rubbn),
where phen is 1,10-phenanthroline, bbn 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 bbn ligands,
were studied in L1210 murine leukaemia cells. Cytotoxicity increased
with linker chain length, and the DD-Rubb16 complex
displayed the highest cytotoxicity of the series, with an IC50
value of 5 mm, 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 bbn bridge of the metal complex. DD-Rubb16 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 bbn series of complexes may have
potential as selective anticancer drugs.
Item Details
Item Type: | Refereed Article |
---|---|
Keywords: | apoptosis, bioinorganic chemistry, cellular uptake, cytotoxicity, ruthenium polypyridyl complexes |
Research Division: | Biomedical and Clinical Sciences |
Research Group: | Immunology |
Research Field: | Immunology not elsewhere classified |
Objective Division: | Health |
Objective Group: | Clinical health |
Objective Field: | Clinical health not elsewhere classified |
UTAS Author: | Korner, H (Professor Heinrich Korner) |
ID Code: | 72466 |
Year Published: | 2011 |
Web of Science® Times Cited: | 62 |
Deposited By: | Menzies Institute for Medical Research |
Deposited On: | 2011-08-26 |
Last Modified: | 2012-03-26 |
Downloads: | 0 |
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