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KMID : 0606920110190020187
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Biomolecules & Therapeutics
2011 Volume.19 No. 2 p.187 ~ p.194
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Anti-Proliferative Activity of OD78 Is Mediated through Cell Cycle Progression by Upregulation p27kip1 in Rat Aortic Vascular Smooth Muscle Cells
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Tudev Munkhtsetseg
Lim Yong
Park Eun-Seok
Kim Won-Sik
Lim Il-Ho
Kwak Jae-Hwan
Jung Jae-Kyung
Hong Jin-Tae
Yoo Hwan-Soo
Lee Mi-Yea
Pyo Myoung-Yun
Yun Yeo-Pyo
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Abstract
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Atherosclerosis and post-angiography restenosis are associated with intimal thickening and concomitant vascular smooth muscle cell (VSMC) proliferation. Obovatol, a major biphenolic component isolated from the Magnolia obovata leaf, is known to have antiinfl ammatory and anti-tumor activities. The goal of the present study was to enhance the inhibitory effects of obovatol to improve its potential as a preventive or therapeutic agent in atherosclerosis and restenosis. Platelet-derived growth factor (PDGF)-BB-induced proliferation of rat aortic smooth muscle cells (RASMCs) was examined in the presence or absence of a newly synthesized obovatol derivative, OD78. The observed anti-proliferative effect of OD78 was further investigated by cell counting and [3H]-thymidine incorporation assays. Treatment with 1-4 μM OD78 dose-dependently inhibited the proliferation and DNA synthesis of 25 ng/ ml PDGF-BB-stimulated RASMCs. Accordingly, OD78 blocked PDGF-BB-induced progression from the G0/G1 to S phase of the cell cycle in synchronized cells. OD78 decreased the expression levels of CDK4, cyclin E, and cyclin D1 proteins, as well as the phosphorylation of retinoblastoma protein and proliferating cell nuclear antigen; however, it did not change the CDK2 expression level. In addition, OD78 inhibited downregulation of the cyclin-dependent kinase inhibitor (CKI) p27kip1. However, OD78 did not
affect the CKI p21cip1 or phosphorylation of early PDGF signaling pathway. These results suggest that OD78 may inhibit PDGF-BBinduced RASMC proliferation by perturbing cell cycle progression, potentially through p27kip1 pathway activation. Consequently, OD78 may be developed as a potential anti-proliferative agent for the treatment of atherosclerosis and angioplasty restenosis.
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KEYWORD
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Smooth muscle cell, PDGF-BB, p27kip1, Cell cycle, Proliferation
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