The new platinum-based anticancer agent LA-12 induces retinol binding protein 4 in vivo
Status PubMed-not-MEDLINE Jazyk angličtina Země Anglie, Velká Británie Médium electronic
Typ dokumentu časopisecké články
PubMed
22040120
PubMed Central
PMC3221626
DOI
10.1186/1477-5956-9-68
PII: 1477-5956-9-68
Knihovny.cz E-zdroje
- Publikační typ
- časopisecké články MeSH
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.
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