PURPOSE: Inflammation acts as a driving force for the development of cancer. Multiple lines of evidence suggest that nonsteroidal anti-inflammatory drugs, especially those that specifically target cyclooxygenase-2 (COX-2), are effective in preventing certain cancers. The present study was aimed at investigating the antitumor promoting potential of celecoxib in chemically induced mouse skin tumorigenesis, as well as elucidating the underlying molecular mechanisms. MATERIALS AND METHODS: To study the antitumor promoting effects of celecoxib, we used the classical two-stage mouse skin tumorigenesis model that involves initiation with a single application of 7,12-dimethylbenz [alpha]anthracene (DMBA) followed by promotion with repeated applications of 12-O-tetradecanoylphorbol-13-acetate (TPA). The effects of celecoxib on the expression of COX-2, vascular endothelial growth factor (VEGF), p65 and the different isoforms of CCAAT/enhancer binding protein (C/EBP) were examined by performing Western blot analysis. Electrophoretic mobility gel shift assay was used to examine the effects of celecoxib on the TPA-induced DNA binding activities of various transcription factors. RESULTS: Our study revealed that topical application of celecoxib (10micromol) significantly reduced the multiplicity of papillomas in DMBA-initiated and TPA-promoted mouse skin. Pretreatment with celecoxib also diminished the expression of COX-2 and VEGF in the mouse skin papillomas. Pretreatment with celecoxib attenuated DNA binding of transcription factor (C/EBP) in the TPA-stimulated mouse skin. Moreover, celecoxib suppressed the TPA-induced nuclear expression of C/EBPdelta, but not C/EBPbeta, in mouse skin in vivo. CONCLUSION: Our study demonstrates the inhibitory effects of celecoxib on mouse skin tumor promotion, which was associated with a decreased expression of COX-2 and VEGF, as well as inhibition of C/EBP activation.
PURPOSE: Inflammation acts as a driving force for the development of cancer. Multiple lines of evidence suggest that nonsteroidal anti-inflammatory drugs, especially those that specifically target cyclooxygenase-2 (COX-2), are effective in preventing certain cancers. The present study was aimed at investigating the antitumor promoting potential of celecoxib in chemically induced mouse skin tumorigenesis, as well as elucidating the underlying molecular mechanisms. MATERIALS AND METHODS: To study the antitumor promoting effects of celecoxib, we used the classical two-stage mouse skin tumorigenesis model that involves initiation with a single application of 7,12-dimethylbenz [alpha]anthracene (DMBA) followed by promotion with repeated applications of 12-O-tetradecanoylphorbol-13-acetate (TPA). The effects of celecoxib on the expression of COX-2, vascular endothelial growth factor (VEGF), p65 and the different isoforms of CCAAT/enhancer binding protein (C/EBP) were examined by performing Western blot analysis. Electrophoretic mobility gel shift assay was used to examine the effects of celecoxib on the TPA-induced DNA binding activities of various transcription factors. RESULTS: Our study revealed that topical application of celecoxib (10micromol) significantly reduced the multiplicity of papillomas in DMBA-initiated and TPA-promoted mouse skin. Pretreatment with celecoxib also diminished the expression of COX-2 and VEGF in the mouseskin papillomas. Pretreatment with celecoxib attenuated DNA binding of transcription factor (C/EBP) in the TPA-stimulated mouse skin. Moreover, celecoxib suppressed the TPA-induced nuclear expression of C/EBPdelta, but not C/EBPbeta, in mouse skin in vivo. CONCLUSION: Our study demonstrates the inhibitory effects of celecoxib on mouseskin tumor promotion, which was associated with a decreased expression of COX-2 and VEGF, as well as inhibition of C/EBP activation.
Authors: Stephen P Motsko; Karen L Rascati; Anthony J Busti; James P Wilson; Jamie C Barner; Kenneth A Lawson; Jason Worchel Journal: Drug Saf Date: 2006 Impact factor: 5.606
Authors: Aniruddha C Amrite; Surya P Ayalasomayajula; Narayan P S Cheruvu; Uday B Kompella Journal: Invest Ophthalmol Vis Sci Date: 2006-03 Impact factor: 4.799
Authors: Jing Jiao; Tomo-O Ishikawa; Darren S Dumlao; Paul C Norris; Clara E Magyar; Carol Mikulec; Art Catapang; Edward A Dennis; Susan M Fischer; Harvey R Herschman Journal: Mol Cancer Res Date: 2014-07-25 Impact factor: 5.852
Authors: Huei-Chen Lao; Jacqueline K Akunda; Kyung-Soo Chun; Gordon P Flake; Stuart H Yuspa; Robert Langenbach Journal: Carcinogenesis Date: 2012-08-17 Impact factor: 4.944
Authors: Helena Escuin-Ordinas; Mohammad Atefi; Yong Fu; Ashley Cass; Charles Ng; Rong Rong Huang; Sharona Yashar; Begonya Comin-Anduix; Earl Avramis; Alistair J Cochran; Richard Marais; Roger S Lo; Thomas G Graeber; Harvey R Herschman; Antoni Ribas Journal: Mol Oncol Date: 2013-12-01 Impact factor: 6.603