title: In Vitro Evaluation of Oxoplatin: An Oral Platinum(IV) Anticancer Agent.
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 IC(50) 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.
authors: Ludwig Boltzmann Cluster Translational Oncology, Operngasse 6/5, 1010 Vienna, Austria.
authors: Ulrike
authors: U
authors: Olszewski
authors: Florian
authors: F
authors: Ach
authors: Ernst
authors: E
authors: Ulsperger
authors: Gerhard
authors: G
authors: Baumgartner
authors: Robert
authors: R
authors: Zeillinger
authors: Patrick
authors: P
authors: Bednarski
authors: Gerhard
authors: G
authors: Hamilton