annexin 1 induced by anti-inflammatory drugs binds to nf-κb inhibiting its activation anticancer effects should in vitro and in vivo.pdf

NIH Public Access Author Manuscript Cancer Res. Author manuscript; available in PMC 2011 March 15. N Published in final edited form as: I H Cancer Res. 2010 March 15; 70(6): 2379–2388. doi:10.1158/0008-5472.CAN-09-4204. - P A A u Annexin 1 induced by anti-inflammatory drugs binds to NF-κB t h o r inhibiting its activation: Anticancer effects in vitro and in vivo M a n u Zhiquan Zhang, Liqun Huang, Wenping Zhao, and Basil Rigas s c Division of Cancer Prevention, Department of Medicine, Stony Brook University, Stony Brook, NY r i p 11794-8173, USA t Abstract Annexin A1 (ANXA1), a mediator of the anti-inflammatory action of glucocorticoids, is important in cancer development and progression, whereas NF-κB regulates multiple cellular phenomena, some of them associated with inflammation and cancer. We demonstrated that glucocorticoids and the chemopreventive modified NSAIDs, such as nitric oxide donating aspirin (NO-ASA) and N phospho-aspirin, induced ANXA1 in cultured human colon and pancreatic cancer cells. ANXA1 I H associated with NF-κB and suppressed its transcriptional activity by preventing NF-κB binding to - P DNA. The induction of ANXA1 by glucocorticoids was proportional to their anti-inflammatory A A potency, as was the suppression of NF-κB activity, which was accompanied by enhanced u apoptosis and inhibition of cell growth mediated by changes in NF-κB-dependent cell signaling. t h The proposed novel mechanism was operational in the intestinal mucosa of mice treated with o r dexameth