In vitro antitumour and hepatotoxicity profiles of Au(I) and Ag(I) bidentate pyridyl phosphine complexes and relationships to cellular uptake

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Title In vitro antitumour and hepatotoxicity profiles of Au(I) and Ag(I) bidentate pyridyl phosphine complexes and relationships to cellular uptake
Author Liu, Johnson J.; Galettis, Peter; Farr, Alistair; Maharaj, Lenushka; Samarasinha, Hasitha; McGechan, Adam C.; Baguley, Bruce C.; Bowen, Richard; Berners-Price, Sue; McKeage, Mark J.
Journal Name Journal of Inorganic Biochemistry
Editor Dr. J H Dawson (Editor-in-Chief)
Year Published 2008
Place of publication United States
Publisher Elsevier Inc.
Abstract In this study we characterised the in vitro antitumour and hepatotoxicity profiles of a series of Au(I) and Ag(I) bidentate phenyl and pyridyl complexes in a panel of cisplatin-resistant human ovarian cancer cell-lines, and in isolated rat hepatocytes. The gold and silver compounds overcame cisplatin-resistance in the CH1-cisR, 41M-cisR and SKOV-3 cell-lines, and showed cytotoxic potencies strongly correlated with their lipophilicity. Complexes with phenyl or 2-pyridyl ligands had high antitumour and hepatotoxic potency and low selectivity between different cell-lines. Their cytotoxicity profiles were similar to classic mitochondrial poisons and an example of this type of compound was shown to accumulate preferentially in the mitochondria of cancer cells in a manner that depended upon the mitochondrial membrane potential. In contrast, complexes with 3- or 4-pyridyl ligands had low antitumour and hepatotoxic potency and cytotoxicity profiles similar to 2-deoxy-D-glucose. In addition, they showed high selectivity between different cell-lines that was not attributable to variation in uptake in different cell-types. The in vitro hepatotoxic potency of the series of gold and silver compounds varied by over 61-fold and was closely related to their lipophilicity and hepatocyte uptake. In conclusion, Au(I) and Ag(I) bidendate pyridyl phosphine complexes demonstrate activity against cisplatin-resistant human cancer cells and in vitro cytotoxicity that strongly depends upon their lipophilicity. © 2007 Elsevier Inc. All rights reserved.
Peer Reviewed Yes
Published Yes
Alternative URI http://dx.doi.org/10.1016/j.jinorgbio.2007.09.003
Volume 102
Issue Number 2
Page from 303
Page to 310
ISSN 0162-0134
Date Accessioned 2009-05-08
Language en_US
Research Centre Institute for Glycomics
Faculty Faculty of Science, Environment, Engineering and Technology
Subject Biochemistry and Cell Biology
URI http://hdl.handle.net/10072/23449
Publication Type Journal Articles (Refereed Article)
Publication Type Code c1

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