UDN glycoprotein inhibits activator protein-1 and matrix metalloproteinase-9 via blocking of oxygen radicals in HT-29 cells
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The present study was performed to investigate the anti-inflammatory potential of a 116-kDa glycoprotein isolated from Ulmus davidiana Nakai (UDN glycoprotein) in lipopolysaccaride (LPS)-treated cancerous human colon epithelial cells (HT-29 cells). UDN glycoprotein inhibited the production of intracellular superoxide anion (O 2 ·− ), hydrogen peroxides (H2O2), and nitric oxide (NO), whereas normalized the activity of anti-oxidant enzymes [superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX)], accompanying the inhibition of manganese-superoxide dismutases (Mn-SOD) activity in LPS-treated HT-29 cells. In addition, UDN glycoprotein blocked the DNA binding activity of activator protein-1 (AP-1) through suppression of c-Jun and c-Fos activities, respectively. We also evaluated the anti-inflammatory potential of UDN glycoprotein based on the activity of the pro-inflammatory signal mediators [inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and matrix metalloproteinases-9 (MMP-9)]. The results showed that UDN glycoprotein (200 μg/ml) has an inhibitory effect on the activation of iNOS, COX-2, and MMP-9 proteins in the LPS-treated HT-29 cells. From these results, we suggest that UDN glycoprotein is one of the potential anti-inflammatory agents that blocks LPS-mediated inflammatory signal pathway in HT-29 cells. Here, we speculate that UDN glycoprotein could be used as an antioxidative agent for inflammatory gastrointestinal cancers.
KeywordsUDN glycoprotein Manganese-superoxide dismutases Activator protein-1 Matrix metalloproteinases-9 HT-29 cells
This work was supported by the Korea Research Foundation Grant funded by the Korean Government (MOEHRD) (KRF-2005-041-F00082).
- 20.Suzuki M, Hisamatsu T, Podolsky DK (2003) Gamma interferon augments the intracellular pathway for lipopolysaccharide (LPS) recognition in human intestinal epithelial cells through coordinated up-regulation of LPS uptake and expression of the intracellular Toll-like receptor 4-MD-2 complex Infect Immun 71:3503–3511PubMedCrossRefGoogle Scholar
- 27.Lee SJ, Oh PS, Ko JH, Lim K, Lim KT (2004) A 150-kDa glycoprotein isolated from Solanum nigrum L. has cytotoxic and apoptotic effects by inhibiting the effects of protein kinase C alpha, nuclear factor-kappa B and inducible nitric oxide in HCT-116 cells. Cancer Chemother Pharmacol 54: 562–572PubMedCrossRefGoogle Scholar
- 36.Hill KA, Wang KL, Stryker SJ, Gupta R, Weinrach DM, Rao MS (2004) Comparative analysis of cell adhesion molecules, cell cycle regulatory proteins, mismatch repair genes, cyclooxygenase-2, and DPC4 in carcinomas arising in inflammatory bowel disease and sporadic colon cancer. Oncol Rep 11:951–956PubMedGoogle Scholar
- 42.Warner RL, Bhagavathula N, Nerusu KC, Lateef H, Younkin E, Johnson KJ, Varani J (2004) Matrix metalloproteinases in acute inflammation: induction of MMP-3 and MMP-9 in fibroblasts and epithelial cells following exposure to pro-inflammatory mediators in vitro. Exp Mol Pathol 76:189–195PubMedCrossRefGoogle Scholar
- 43.Grau R, Punzon C, Fresno M, Iniguez MA (2006) Peroxisome-proliferator-activated receptor alpha agonists inhibit cyclo-oxygenase 2 and vascular endothelial growth factor transcriptional activation in human colorectal carcinoma cells via inhibition of activator protein-1. Biochem J 395:81–88PubMedCrossRefGoogle Scholar