The new platinum-based anticancer agent LA-12 induces retinol binding protein 4 in vivo

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. © 2011 bouchal et al; licensee biomed central ltd.