Relative non‐steroidal anti‐inflammatory drug (NSAID) antiproliferative activity is mediated through p21‐induced G1 arrest and E2F inhibition

• DOI: 10.1002/mc.20318
• Publication Date: 2007-04-05T21:19:08Z
• Authors: Jonathan M. Bock; Sarita G. Menon; Prabhat C. Goswami; Lori L. Sinclair; Nichole S. Bedford; Frederick E. Domann; Douglas K. Trask
• Keywords: Celecoxib; Sulindac; Flurbiprofen; Ibuprofen; Mechanism of Action

Abstract This study was performed to compare the relative antineoplastic activity of 10 different non‐steroidal anti‐inflammatory drugs (NSAIDs) in clinical use, and investigate underlying mechanisms this a squamous cell carcinoma head neck model (SCCHN). A standard 5‐day MTT assay used calculate IC 50 values UM‐SCC‐1 cells for NSAIDs, including celecoxib, rofecoxib, sulindac sulfide, sulfone, indomethacin, ketoprofen, flurbiprofen, naproxen, piroxicam, aspirin. Celecoxib, COX‐2 specific inhibitor, by far most potent NSAID, with an 39.9 ± 1.1 µM, followed sulfide (116.5 2.34 µM). Celecoxib also induced more activation caspase‐3 than any other NSAID. Cell cycle analysis showed that celecoxib both 3‐fold increase G 1 phase distribution, correlated strong induction p21 waf1/cip1 , inhibition cyclin D1, hypophosphorylation Rb. treatment downstream E2F transactivating as determined luciferase reporter assay. These data demonstrate wide range various NSAID agents, reveal mechanism action through apoptosis. © 2007 Wiley‐Liss, Inc.