PMID- 21811927 OWN - NLM STAT- MEDLINE DCOM- 20120131 LR - 20110803 IS - 1976-3786 (Electronic) IS - 0253-6269 (Linking) VI - 34 IP - 7 DP - 2011 Jul TI - Inhibitory effects of OD 78 [3-(4-bromo-phenoxy)-4,5-dihydroxybenzoic acid-methyl ester] on the proliferation and migration of TNF-alpha-induced rat aortic smooth muscle cells. PG - 1191-9 LID - 10.1007/s12272-011-0718-7 [doi] AB - The proliferation and migration of vascular smooth muscle cells (VSMCs) play important roles in the formation and progression of intimal thickening in early-phase atherosclerosis and in restenosis after vascular injury. Tumor necrosis factor-alpha (TNF-alpha) is released from macrophages in atherosclerotic lesions and from neointimal vascular smooth muscle cells after balloon-injury. Obovatol, a major biphenolic component isolated from the Magnolia obovata leaf, is known to have anti-inflammatory and antitumor activities. The goal of this study was to examine the cardioprotective effects of the obovatol derivative OD 78 on the TNF-alpha-induced proliferation and migration of rat aortic smooth muscle cells (RASMCs). The antiproliferative effects of OD 78 on RASMCs were examined by cell counting and [(3)H]-thymidine incorporation assays. Treatment of cells with 1-4 muM OD 78 inhibited the proliferation and DNA synthesis of TNF-alpha-stimulated RASMCs in a concentration-dependent manner, without cytotoxicity. Treatment with OD 78 inhibited TNF-alpha-mediated p38 phosphorylation, but did not change the activation of extracellular signal-regulated kinase or c-Jun N-terminal kinase. Furthermore, treatment with OD 78 decreased TNF-alpha-induced levels of cyclin E, cyclin D1, CDK2, proliferating cell nuclear antigen, and phosphorylated retinoblastoma protein, but not the CDK4 expression level. Also, OD 78 inhibits the migration of TNF-alpha-induced RASMC in transwells. OD 78 treatment strongly decreased matrix metalloproteinase-9 (MMP-9) expression in a dose-dependent manner, but the MMP-2 expression was unchanged. These results show that OD 78 may be developed as a potential antiproliferative agent for the treatment of angioplasty restenosis and atherosclerosis. FAU - Lim, Yong AU - Lim Y AD - Department of Clinical Laboratory Science, Dong-eui University, Busan 614-714, Korea. FAU - Tudev, Munkhtsetseg AU - Tudev M FAU - Park, Eun-Seok AU - Park ES FAU - Kim, Won-Shik AU - Kim WS FAU - Lim, Il-Ho AU - Lim IH FAU - Lee, Mi-Yea AU - Lee MY FAU - Lee, Heesoon AU - Lee H FAU - Jung, Jae-Kyung AU - Jung JK FAU - Hong, Jin-Tae AU - Hong JT FAU - Yoo, Hwan-Soo AU - Yoo HS FAU - Lee, Myung-Koo AU - Lee MK FAU - Pyo, Myoung-Yun AU - Pyo MY FAU - Yun, Yeo-Pyo AU - Yun YP LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20110803 PL - Korea (South) TA - Arch Pharm Res JT - Archives of pharmacal research JID - 8000036 RN - 0 (3-(4-bromo-phenoxy)-4,5-dihydroxybenzoic acid-methyl ester) RN - 0 (Benzoates) RN - 0 (Cardiotonic Agents) RN - 0 (Cyclin E) RN - 0 (Phenyl Ethers) RN - 0 (Retinoblastoma Protein) RN - 0 (Tumor Necrosis Factor-alpha) RN - 9007-49-2 (DNA) RN - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1) SB - IM MH - Animals MH - Aorta/cytology/drug effects MH - Benzoates/metabolism/*pharmacology MH - Cardiotonic Agents/metabolism/*pharmacology MH - Cell Cycle/drug effects MH - Cell Movement/drug effects MH - Cell Proliferation/*drug effects MH - Cyclin E/metabolism MH - DNA/analysis/biosynthesis MH - Extracellular Signal-Regulated MAP Kinases/metabolism MH - Mitogen-Activated Protein Kinase 1/metabolism MH - Muscle, Smooth, Vascular/cytology/*drug effects/metabolism MH - Myocytes, Smooth Muscle/*drug effects/physiology MH - Phenyl Ethers/metabolism/*pharmacology MH - Phosphorylation/drug effects MH - Rats MH - Retinoblastoma Protein/metabolism MH - Tumor Necrosis Factor-alpha/metabolism EDAT- 2011/08/04 06:00 MHDA- 2012/02/01 06:00 CRDT- 2011/08/04 06:00 PHST- 2010/12/08 00:00 [received] PHST- 2011/03/29 00:00 [accepted] PHST- 2011/03/21 00:00 [revised] PHST- 2011/08/04 06:00 [entrez] PHST- 2011/08/04 06:00 [pubmed] PHST- 2012/02/01 06:00 [medline] AID - 10.1007/s12272-011-0718-7 [doi] PST - ppublish SO - Arch Pharm Res. 2011 Jul;34(7):1191-9. doi: 10.1007/s12272-011-0718-7. Epub 2011 Aug 3.