Table of Contents 
Metal-Based Drugs
Volume 2009, Article ID 348916, 11 pages
http://dx.doi.org/10.1155/2009/348916
Research Article

In Vitro Evaluation of Oxoplatin: An Oral Platinum(IV) Anticancer Agent

Ulrike Olszewski,1,2 Florian Ach,1,2 Ernst Ulsperger,1 Gerhard Baumgartner,1 Robert Zeillinger,1,2 Patrick Bednarski,3 and Gerhard Hamilton1,2

1Ludwig Boltzmann Cluster Translational Oncology, Operngasse 6/5, 1010 Vienna, Austria
2Medical University of Vienna, Department of Gynecology, Waehringer Guertel 18-20, 1090 Vienna, Austria
3Institute of Pharmacy, University of Greifswald, Friedrich-Ludwig-Jahn-Strasse 17, 17487 Greifswald, Germany

Received 25 November 2008; Revised 23 February 2009; Accepted 15 April 2009

Academic Editor: Mauro Coluccia

Copyright © 2009 Ulrike Olszewski et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Platinum(IV) compounds like oxoplatin (cis, cis, trans-diammine-dichlorido-dihydroxido-platinum(IV)) show increased stability and therefore can be applied orally. In a panel of 38 human cancer cell lines this drug induced S-phase arrest and cell death with IC50 values 2.5-fold higher than cisplatin. Oxoplatin may be converted to cisplatin by intracellular reducing agents, however, exposure to 0.1 M HCl mimicking gastric acid yielded cis-diammine-tetrachlorido-platinum(IV) exhibiting twofold increased activity. Similar results were obtained for another platinum(IV) compound, JM 149 (ammine-dichlorido-(cyclohexylamine)-dihydroxido-platinum(IV)), but not for its parent drug JM 216/satraplatin. Genome-wide expression profiling of H526 small cell lung cancer cells treated with these platinum species revealed clear differences in the expression pattern of affected genes between oxoplatin and cisplatin. In conclusion, oxoplatin constitutes a potent oral agent that is either reduced or converted to distinct active compounds, for example, by gastric acid or acidic areas prevailing in solid tumors, in dependence of the respective pharmaceutical formulation.