Proteomic (antibody microarray) exploration of the molecular mechanism of action of the specific COX-2 inhibitor DuP 697.

Proteomic (antibody microarray) exploration of the molecular mechanism of action of the specific COX-2 inhibitor DuP 697.

Int J Oncol. 2013 Jan 22;

Authors: Agarwal V, Hodgkinson VC, Eagle GL, Scaife L, Lind MJ, Cawkwell L

Abstract
We have previously shown that specific COX-2 inhibitors, including DuP�697, have anti-proliferative effects on mesothelioma cells and potentiate the cytotoxicity of pemetrexed. Here, we used a novel proteomic approach to explore the mechanism of action of this agent. COX-2-positive cell lines MSTO-211H (mesothelioma) and A549 (lung cancer) were exposed to DuP�697 for 72 h. Drug carrier only was added to control cells. Extracted proteins from treated and control cells were analysed using a comparative proteomic platform. Differentially expressed proteins, identified by the Panorama Xpress Profiler725 antibody microarray were submitted to Ingenuity Pathway Analysis. A total of 32 unique differentially expressed proteins were identified with a significant (>1.8-fold) difference in expression between treated and untreated cells in at least one cell line. Five molecules, BCL2L1 (Bcl-xL), BID, CHUK (IKK), FASLG and RAF1, were mapped to the Apoptosis Signaling pathway following Ingenuity Pathway Analysis. BCL2L1 (Bcl-xL) and BID were analysed using immuno-blotting and differential expression was confirmed. Proteomic (antibody microarray) analysis suggests that the mechanism of action of DuP�697 may be exerted via the induction of apoptosis. The antibody microarray platform can be utilised to explore the molecular mechanism of action of novel anticancer agents.

PMID: 23338544 [PubMed - as supplied by publisher]

dna-pk coxinhibitors c-met inhibitors