PMID- 18801463 OWN - NLM STAT- MEDLINE DCOM- 20090423 LR - 20231213 IS - 1567-5769 (Print) IS - 1567-5769 (Linking) VI - 8 IP - 13-14 DP - 2008 Dec 20 TI - Signaling pathway for TNF-alpha-induced MMP-9 expression: mediation through p38 MAP kinase, and inhibition by anti-cancer molecule magnolol in human urinary bladder cancer 5637 cells. PG - 1821-6 LID - 10.1016/j.intimp.2008.08.018 [doi] AB - We investigated the molecular mechanisms involved in the expression of matrix metalloproteinase-9 (MMP-9) and the inhibition of MMP expression by magnolol in 5637 human urinary bladder cancer cells. Tumor necrosis factor-alpha (TNF-alpha) stimulated the secretion of MMP-9 in 5637 cells, as shown by zymography and promoter assay. The transcription factor nuclear factor kappaB (NF-kappaB) binding site was identified by gel-shift assay to be a cis-element for TNF-alpha activation of the MMP-9 promoter. Our results also demonstrated that TNF-alpha stimulates MMP-9 expression via the p38 MAP kinase signaling pathway in 5637 cells. Moreover, p38 MAP kinase-mediated MMP-9 gene regulation in response to TNF-alpha is involved in the NF-kappaB response element in 5637 cells. In addition, magnolol inhibited TNF-alpha-induced expression of the MMP-9, as determined by zymography and immunoblot, in 5637 cells. The TNF-alpha-induced invasion and migration of cells was inhibited by magnolol, as assessed by a modified boyden chamber and wound-healing assays, respectively. Finally, magnolol blocked MMP-9 expression, at least in part, by decreasing the binding of transcription factor NF-kappaB to DNA. In conclusion, TNF-alpha induced MMP-9 expression in 5637 cells by activating the transcription factor NF-kappaB, which is involved in the p38 MAP kinase-mediated control of MMP-9 regulation. Magnolol inhibited MMP-9 expression through the transcription factor NF-kappaB in TNF-alpha-induced 5637 cells. FAU - Lee, Se-Jung AU - Lee SJ AD - Department of Food and Biotechnology, Chungju National University, Chungju, Chungbuk 380-702, South Korea. FAU - Park, Sung-Soo AU - Park SS FAU - Lee, Ung-Soo AU - Lee US FAU - Kim, Wun-Jae AU - Kim WJ FAU - Moon, Sung-Kwon AU - Moon SK LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20080916 PL - Netherlands TA - Int Immunopharmacol JT - International immunopharmacology JID - 100965259 RN - 0 (Antineoplastic Agents) RN - 0 (Biphenyl Compounds) RN - 0 (Enzyme Inhibitors) RN - 0 (Imidazoles) RN - 0 (Lignans) RN - 0 (Matrix Metalloproteinase Inhibitors) RN - 0 (Pyridines) RN - 0 (Tumor Necrosis Factor-alpha) RN - 001E35HGVF (magnolol) RN - EC 2.7.11.1 (Protein Serine-Threonine Kinases) RN - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases) RN - OU13V1EYWQ (SB 203580) SB - IM MH - Antineoplastic Agents/*pharmacology MH - Biphenyl Compounds/*pharmacology MH - Cell Line, Tumor MH - Cell Movement/drug effects MH - Enzyme Inhibitors/*pharmacology MH - Humans MH - Imidazoles/pharmacology MH - Lignans/*pharmacology MH - *Matrix Metalloproteinase Inhibitors MH - Protein Serine-Threonine Kinases/drug effects/metabolism MH - Pyridines/pharmacology MH - Signal Transduction/drug effects MH - Tumor Necrosis Factor-alpha/pharmacology MH - Urinary Bladder Neoplasms/*enzymology MH - p38 Mitogen-Activated Protein Kinases/metabolism MH - NF-kappaB-Inducing Kinase EDAT- 2008/09/20 09:00 MHDA- 2009/04/25 09:00 CRDT- 2008/09/20 09:00 PHST- 2008/04/24 00:00 [received] PHST- 2008/08/26 00:00 [revised] PHST- 2008/08/26 00:00 [accepted] PHST- 2008/09/20 09:00 [pubmed] PHST- 2009/04/25 09:00 [medline] PHST- 2008/09/20 09:00 [entrez] AID - S1567-5769(08)00269-5 [pii] AID - 10.1016/j.intimp.2008.08.018 [doi] PST - ppublish SO - Int Immunopharmacol. 2008 Dec 20;8(13-14):1821-6. doi: 10.1016/j.intimp.2008.08.018. Epub 2008 Sep 16.