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In vitro antitumour and hepatotoxicity profiles of Au(I) and Ag(I) bidentate pyridyl phosphine complexes and relationships to cellular uptake
Liu, JJ and Galettis, P and Farr, A and Maharaj, L and Samarasinha, H and McGechan, AC and Baguley, BC and Bowen, RJ and Berners-Price, SJ and McKeage, MJ, In vitro antitumour and hepatotoxicity profiles of Au(I) and Ag(I) bidentate pyridyl phosphine complexes and relationships to cellular uptake, Journal of Inorganic Biochemistry, 102, (2) pp. 303-310. ISSN 0162-0134 (2008) [Refereed Article]
Copyright 2007 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.
|Item Type:||Refereed Article|
|Keywords:||antitumour activity, gold- silver-phosphines, uptake|
|Research Division:||Biomedical and Clinical Sciences|
|Research Group:||Pharmacology and pharmaceutical sciences|
|Research Field:||Pharmaceutical sciences|
|Objective Group:||Clinical health|
|Objective Field:||Clinical health not elsewhere classified|
|UTAS Author:||Liu, JJ (Dr Johnson Liu)|
|Web of Science® Times Cited:||164|
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