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

Author:

Olszewski Ulrike12,Ach Florian12,Ulsperger Ernst1,Baumgartner Gerhard1,Zeillinger Robert12,Bednarski Patrick3,Hamilton Gerhard12

Affiliation:

1. Ludwig Boltzmann Cluster Translational Oncology, Operngasse 6/5, 1010 Vienna, Austria

2. Medical University of Vienna, Department of Gynecology, Waehringer Guertel 18-20, 1090 Vienna, Austria

3. Institute of Pharmacy, University of Greifswald, Friedrich-Ludwig-Jahn-Strasse 17, 17487 Greifswald, Germany

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 withIC50values 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.

Publisher

Hindawi Limited

Subject

Inorganic Chemistry,Drug Discovery,Pharmacology,Toxicology

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