title: Inhibitory effects of OD 78 [3-(4-bromo-phenoxy)-4,5-dihydroxybenzoic acid-methyl ester] on the proliferation and migration of TNF-α-induced rat aortic smooth muscle cells.
abstract: 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-α (TNF-α) 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-α-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 μM OD 78 inhibited the proliferation and DNA synthesis of TNF-α-stimulated RASMCs in a concentration-dependent manner, without cytotoxicity. Treatment with OD 78 inhibited TNF-α-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-α-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-α-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.
authors.affiliation: Department of Clinical Laboratory Science, Dong-eui University, Busan 614-714, Korea.
authors.forename: Yong
authors.initials: Y
authors.lastname: Lim
authors.forename: Munkhtsetseg
authors.initials: M
authors.lastname: Tudev
authors.forename: Eun-Seok
authors.initials: ES
authors.lastname: Park
authors.forename: Won-Shik
authors.initials: WS
authors.lastname: Kim
authors.forename: Il-Ho
authors.initials: IH
authors.lastname: Lim
authors.forename: Mi-Yea
authors.initials: MY
authors.lastname: Lee
authors.forename: Heesoon
authors.initials: H
authors.lastname: Lee
authors.forename: Jae-Kyung
authors.initials: JK
authors.lastname: Jung
authors.forename: Jin-Tae
authors.initials: JT
authors.lastname: Hong
authors.forename: Hwan-Soo
authors.initials: HS
authors.lastname: Yoo
authors.forename: Myung-Koo
authors.initials: MK
authors.lastname: Lee
authors.forename: Myoung-Yun
authors.initials: MY
authors.lastname: Pyo
authors.forename: Yeo-Pyo
authors.initials: YP
authors.lastname: Yun
mesh_terms: D000818:Animals; D001011:Aorta / Q000166:cytology / Q000187:drug effects; D001565:Benzoates / Q000378:metabolism / Q000494:pharmacology*; D002316:Cardiotonic Agents / Q000378:metabolism / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D019927:Cyclin E / Q000378:metabolism; D004247:DNA / Q000032:analysis / Q000096:biosynthesis; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000502:physiology; D010647:Phenyl Ethers / Q000378:metabolism / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D016160:Retinoblastoma Protein / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: C569594:3-(4-bromo-phenoxy)-4,5-dihydroxybenzoic acid-methyl ester; D001565:Benzoates; D002316:Cardiotonic Agents; D019927:Cyclin E; D010647:Phenyl Ethers; D016160:Retinoblastoma Protein; D014409:Tumor Necrosis Factor-alpha; D004247:DNA; D048049:Extracellular Signal-Regulated MAP Kinases; D019950:Mitogen-Activated Protein Kinase 1