The New Platinum-Based Anticancer Agent LA12 Induces Retinol Binding Protein 4 In Vivo
Bouchal, P., Jarkovsky, J., Hrazdilova, K., Mudrochova, M., Struharova, I., Hernychova, L., Damborsky, J., Sova, P., Vojtesek, B.
PROTEOME SCIENCE 9: 68-77 (2011)
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 which could potentially 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) for 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 plasma retinol binding protein RBP4 as a protein correlating with LA-12 level in both rat plasma and plasma ultrafiltrate. Similar trend was observed for randomly selected patients involved in Phase I of 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.