Research
The new platinum-based anticancer agent LA-12 induces retinol binding protein 4 in vivo
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* Corresponding author: Borivoj Vojtesek vojtesek@mou.cz
1 Masaryk University, Faculty of Science, Department of Biochemistry, Kotlarska 2, 611 37 Brno, Czech Republic
2 Masaryk Memorial Cancer Institute, Regional Centre for Applied Molecular Oncology, Zluty kopec 7, 656 53 Brno, Czech Republic
3 Masaryk University, Institute of Biostatistics and Analyses, Kamenice 3, 625 00 Brno, Czech Republic
4 Masaryk Memorial Cancer Institute, Department of Oncological and Experimental Pathology, Zluty kopec 7, 656 53 Brno, Czech Republic
5 University of Defence, Faculty of Military Health Sciences, Institute of Molecular Pathology, Trebesska 1575, 500 03 Hradec Kralove, Czech Republic
6 Masaryk University, Faculty of Science, Department of Experimental Biology, Kamenice 5, 625 00 Brno, Czech Republic
7 Centre of Biomolecular and Cellular Engineering, International Clinical Research Center, St. Anne's University Hospital Brno, Pekarska 53, 656 91 Brno, Czech Republic
8 Platinum Pharmaceuticals a.s., Karasek 1, 621 33 Brno, Czech Republic
Proteome Science 2011, 9:68 doi:10.1186/1477-5956-9-68
Published: 31 October 2011Abstract
Background
The initial pharmacokinetic study of a new anticancer agent (OC-6-43)-bis(acetato)(1-adamantylamine)amminedichloroplatinum (IV) (LA-12) was complemented by proteomic screening of rat plasma. The objective of the study was to identify new LA-12 target proteins that serve as markers of LA-12 treatment, response and therapy monitoring.
Methods
Proteomic profiles were measured by surface-enhanced laser desorption-ionization time-of-flight mass spectrometry (SELDI-TOF MS) in 72 samples of rat plasma randomized according to LA-12 dose and time from administration. Correlation of 92 peak clusters with platinum concentration was evaluated using Spearman correlation analysis.
Results
We identified Retinol-binding protein 4 (RBP4) whose level correlated with LA-12 level in treated rats. Similar results were observed in randomly selected patients involved in Phase I clinical trials.
Conclusions
RBP4 induction is in agreement with known RBP4 regulation by amantadine and cisplatin. Since retinol metabolism is disrupted in many cancers and inversely associates with malignancy, these data identify a potential novel mechanism for the action of LA-12 and other similar anti-cancer drugs.