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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

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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 [3H]-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.

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Authors and Affiliations

  1. Department of Clinical Laboratory Science, Dong-eui University, Busan, 614-714, Korea

    Yong Lim

  2. College of Pharmacy, Research Center for Bioresource and Health, Chungbuk National University, Cheongju, 361-763, Korea

    Munkhtsetseg Tudev, Eun-Seok Park, Won-Shik Kim, Il-Ho Lim, Heesoon Lee, Jae-Kyung Jung, Jin-Tae Hong, Hwan-Soo Yoo, Myung-Koo Lee & Yeo-Pyo Yun

  3. Department of Social Welfare, World Cyber College, Gwangju, 464-895, Korea

    Mi-Yea Lee

  4. College of Pharmacy, Sookmyung Women’s University, Seoul, 140-742, Korea

    Myoung-Yun Pyo

  5. College of Pharmacy, Chungbuk National University, Cheongju, 361-763, Korea

    Yeo-Pyo Yun

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  1. Yong Lim
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  2. Munkhtsetseg Tudev
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Correspondence to Yeo-Pyo Yun.

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These authors contributed equally to this work.

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Lim, Y., Tudev, M., Park, ES. et al. 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. Arch. Pharm. Res. 34, 1191–1199 (2011). https://doi.org/10.1007/s12272-011-0718-7

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  • DOI: https://doi.org/10.1007/s12272-011-0718-7

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