dc.contributor.author |
Liu, Johnson |
en |
dc.contributor.author |
Galettis, P |
en |
dc.contributor.author |
Farr, A |
en |
dc.contributor.author |
Maharaj, L |
en |
dc.contributor.author |
Samarasingha, H |
en |
dc.contributor.author |
McGechan, AC |
en |
dc.contributor.author |
Baguley, Bruce |
en |
dc.contributor.author |
Bowen, RJ |
en |
dc.contributor.author |
Berners-Price, SJ |
en |
dc.contributor.author |
McKeage, Mark |
en |
dc.date.accessioned |
2012-03-01T21:09:18Z |
en |
dc.date.issued |
2008 |
en |
dc.identifier.citation |
J INORG BIOCHEM 102(2):303-310 Feb 2008 |
en |
dc.identifier.issn |
0162-0134 |
en |
dc.identifier.uri |
http://hdl.handle.net/2292/12521 |
en |
dc.description.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. |
en |
dc.publisher |
Elsevier |
en |
dc.relation.ispartofseries |
Journal of Inorganic Biochemistry |
en |
dc.rights |
Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. |
en |
dc.rights.uri |
https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm |
en |
dc.title |
In vitro antitumour and hepatotoxicity profiles of Au(I) and Ag(I) bidentate pyridyl phosphine complexes and relationships to cellular uptake |
en |
dc.type |
Journal Article |
en |
dc.identifier.doi |
10.1016/j.jinorgbio.2007.09.003 |
en |
pubs.issue |
2 |
en |
pubs.begin-page |
303 |
en |
pubs.volume |
102 |
en |
dc.rights.holder |
Copyright: Elsevier |
en |
dc.identifier.pmid |
18029019 |
en |
pubs.end-page |
310 |
en |
dc.rights.accessrights |
http://purl.org/eprint/accessRights/RestrictedAccess |
en |
pubs.subtype |
Article |
en |
pubs.elements-id |
72596 |
en |
pubs.org-id |
Medical and Health Sciences |
en |
pubs.org-id |
Medical Sciences |
en |
pubs.org-id |
Pharmacology |
en |
pubs.org-id |
Science |
en |
pubs.org-id |
Science Research |
en |
pubs.org-id |
Maurice Wilkins Centre (2010-2014) |
en |
pubs.record-created-at-source-date |
2010-09-01 |
en |
pubs.dimensions-id |
18029019 |
en |