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ZJUS-B
Journal of Zhejiang University-SCIENCE B (Biomedicine & Biotechnology)  2009, Vol. 10 Issue (7): 528-535    DOI: 10.1631/jzus.B0820351
Biomedicine     
Parthenolide inhibits proliferation of vascular smooth muscle cells through induction of G0/G1 phase cell cycle arrest
Shao-xiang WENG, Mei-hua SUI, Shan CHEN, Jian-an WANG, Geng XU, Ji MA, Jiang SHAN, Lu FANG
Department of Cardiology, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China; Department of Chemical and Biochemical Engineering, Zhejiang University, Hangzhou 310027, China; Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, SC 29425, USA
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Abstract  Objective: This study is to determine the effect of the natural product parthenolide, a sesquiterpene lactone isolated from extracts of the herb Tanacetum parthenium, on the proliferation of vascular smooth muscle cells (VSMCs). Methods: Rat aortic VSMCs were isolated and cultured in vitro, and treated with different concentrations of parthenolide (10, 20 and 30 μmol/L). [3H]thymidine incorporation was used as an index of cell proliferation. Cell cycle progression and distribution were determined by flow cytometric analysis. Furthermore, the expression of several regulatory proteins relevant to VSMC proliferation including IκBα, cyclooxygenase-2 (Cox-2), p21, and p27 was examined to investigate the potential molecular mechanism. Results: Treatment with parthenolide significantly decreased the [3H]thymidine incorporation into DNA by 30%~56% relative to control values in a dose-dependent manner (P<0.05). Addition of parthenolide also increased cell population at G0/G1 phase by 19.2%~65.7% (P<0.05) and decreased cell population at S phase by 50.7%~84.8% (P<0.05), which is consistent with its stimulatory effects on p21 and p27. In addition, parthenolide also increased IκBα expression and reduced Cox-2 expression in a time-dependent manner. Conclusion: Our results show that parthenolide significantly inhibits the VSMC proliferation by inducing G0/G1 cell cycle arrest. IκBα and Cox-2 are likely involved in such inhibitory effect of parthenolide on VSMC proliferation. These findings warrant further investigation on potential therapeutic implications of parthenolide on VSMC proliferation in vivo.

Key words： Parthenolide      Vascular smooth muscle cell (VSMC)      Cell proliferation      IκBα      Cyclooxygenase-2 (Cox-2)      p21     
Received: 02 November 2008     
CLC:  R54  
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Shao-xiang WENG
Mei-hua SUI
Shan CHEN
Jian-an WANG
Geng XU
Ji MA
Jiang SHAN
Lu FANG
Cite this article:

Shao-xiang WENG, Mei-hua SUI, Shan CHEN, Jian-an WANG, Geng XU, Ji MA, Jiang SHAN, Lu FANG. Parthenolide inhibits proliferation of vascular smooth muscle cells through induction of G0/G1 phase cell cycle arrest. Journal of Zhejiang University-SCIENCE B (Biomedicine & Biotechnology), 2009, 10(7): 528-535.

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http://www.zjujournals.com/xueshu/zjus-b/10.1631/jzus.B0820351     OR     http://www.zjujournals.com/xueshu/zjus-b/Y2009/V10/I7/528

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