The new platinum-based anticancer agent LA-12 induces retinol binding protein 4 in vivo
Open Access
- 31 October 2011
- journal article
- research article
- Published by Springer Science and Business Media LLC in Proteome Science
- Vol. 9 (1), 68
- https://doi.org/10.1186/1477-5956-9-68
Abstract
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.Keywords
This publication has 32 references indexed in Scilit:
- The new platinum(IV) derivative LA-12 shows stronger inhibitory effect on Hsp90 function compared to cisplatinMolecular Cancer, 2010
- The effect of cellular environment and p53 status on the mode of action of the platinum derivative LA-12Investigational New Drugs, 2009
- Surface-enhanced laser desorption/ionization time-of-flight proteomic profiling of breast carcinomas identifies clinicopathologically relevant groups of patients similar to previously defined clusters from cDNA expressionBreast Cancer Research, 2008
- Novel Anticancer Platinum(IV) Complexes with Adamantylamine: Their Efficiency and Innovative Chemotherapy Strategies Modifying Lipid MetabolismMetal-Based Drugs, 2008
- The novel platinum(IV) complex LA-12 induces p53 and p53/47 responses that differ from the related drug, cisplatinAnti-Cancer Drugs, 2008
- Different cell cycle modulation following treatment of human ovarian carcinoma cells with a new platinum(IV) complex vs cisplatinInvestigational New Drugs, 2007
- Surface-Enhanced Laser Desorption Ionization/Time-of-Flight Mass Spectrometry Reveals Significant Artifacts in Serum Obtained from Clot Activator–Containing Collection DevicesClinical Chemistry, 2006
- Cisplatin: mode of cytotoxic action and molecular basis of resistanceOncogene, 2003
- Platinum‐based anticancer agents: Innovative design strategies and biological perspectivesMedicinal Research Reviews, 2003
- Crystal Structure of the Trigonal Form of Human Plasma Retinol-binding Protein at 2·5 Å ResolutionJournal of Molecular Biology, 1993