eCite Digital Repository
In vitro antitumour and hepatotoxicity profiles of Au(I) and Ag(I) bidentate pyridyl phosphine complexes and relationships to cellular uptake
Citation
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 Statement
Copyright 2007 Elsevier Inc.
DOI: doi:10.1016/j.jinorgbio.2007.09.003
Abstract
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 Details
| 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 Division: | Health |
| Objective Group: | Clinical health |
| Objective Field: | Clinical health not elsewhere classified |
| UTAS Author: | Liu, JJ (Dr Johnson Liu) |
| ID Code: | 89125 |
| Year Published: | 2008 |
| Web of Science® Times Cited: | 164 |
| Deposited By: | Pharmacy |
| Deposited On: | 2014-02-25 |
| Last Modified: | 2017-01-09 |
| Downloads: | 0 |
Repository Staff Only: item control page