Parthenolide inhibits proliferation of vascular smooth muscle cells through induction of G0/G1 phase cell cycle arrest |
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| Authors: | Shao-xiang Weng Mei-hua Sui Shan Chen Jian-an Wang Geng Xu Ji Ma Jiang Shan Lu Fang |
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| Institution: | (1) Department of Cardiology, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310009, China;(2) Department of Chemical and Biochemical Engineering, Zhejiang University, Hangzhou, 310027, China;(3) 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.
Project (No. 491020-W50315) supported by the Foundation of the Health Bureau of Zhejiang, China |
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| Keywords: | Parthenolide Vascular smooth muscle cell (VSMC) Cell proliferation Iκ Bα Cyclooxygenase-2 (Cox-2) p21 |
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