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http://dspace.mediu.edu.my:8181/xmlui/handle/10261/5049| Title: | Peroxisome-proliferator-activated receptor a agonists inhibit cyclo-oxygenase 2 and vascular endothelial growth factor transcriptional activation in human colorectal carcinoma cells via inhibition of activator protein-1 |
| Authors: | Ministerio de Educación y Ciencia (España) European Commission Red Temática de Investigación Cooperativa en Enfermedades Cardiovasculares (España) Fondo de Investigación Sanitaria (España) Esteve Comunidad de Madrid Fundación Ramón Areces European Commission |
| Keywords: | Peroxisome-proliferator-activated receptor a (PPARa) Cyclo-oxygenase 2 (COX-2) LY-171883 SW620 cell Vascular endothelial growth factor (VEGF) WY-14,643 |
| Publisher: | Portland Press |
| Description: | Article available at http://dx.doi.org/10.1042/BJ20050964 Recent evidence indicates that PPAR (peroxisome-proliferator-activated receptor) a ligands possess anti-inflammatory and antitumoural properties owing to their inhibitory effects on the expression of genes that are involved in the inflammatory response. However, the precise molecular mechanisms underlying these effects are poorly understood. In the present study, we show that tumour promoter PMA-mediated induction of genes that are significantly associated with inflammation, tumour growth and metastasis, such as COX-2 (cyclo-oxygenase 2) and VEGF (vascular endothelial growth factor), is inhibited by PPARa ligands in the human colorectal carcinoma cell line SW620. PPARa activators LY-171883 and WY-14,643 were able to diminish transcriptional induction of COX-2 and VEGF by inhibiting AP-1 (activator protein-1)-mediated transcriptional activation induced by PMA or by c-Jun overexpression. The actions of these ligands on AP-1 activation and COX-2 and VEGF transcriptional induction were found to be dependent on PPARa expression. Our studies demonstrate the existence of a negative cross-talk between the PPARa- and AP-1-dependent signalling pathways in these cells. PPARa interfered with at least two steps within the pathway leading to AP-1 activation. First, PPARa activation impaired AP-1 binding to a consensus DNA sequence. Secondly, PPARa ligands inhibited c-Jun transactivating activity. Taken together, these findings provide new insight into the anti-inflammatory and anti-tumoural properties of PPARa activation, through the inhibition of the induction of AP-1-dependent genes that are involved in inflammation and tumour progression This work was supported by grants from the Ministerio de Educación y Ciencia-FEDER (Fondo Europeo de Desarrollo Regional) (SAF2004-05109) and (BFU2004-04157); RECAVA (Red Temática de Enfermedades Cardiovasculares) cardiovascular network (C03/01) from Fondo de Investigaciones Sanitarias; Laboratorios del Dr Esteve; Comunidad de Madrid (08.3/0007/1) and Fundación Ramón Areces. This research was also supported by ECFP6 (European Commission Sixth Framework Programme) funding; EICOSANOX (eicosanoids and nitric oxide) integrated project (LSHCT- 2004-0050333); and MAIN (migration and inflammation) network of excellence. The Commission is not liable for any use that may be made of information herein. M.A. I. is a recipient of the Ramón y Cajal Program of the Ministerio de Educación y Ciencia of Spain Peer reviewed |
| URI: | http://dspace.mediu.edu.my:8181/xmlui/handle/10261/5049 |
| Other Identifiers: | Biochem. J. (2006) 395 (81–88) 0264-6021 (Print) 1470-8728 (Online) http://hdl.handle.net/10261/5049 |
| Appears in Collections: | Digital Csic |
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