Artesunate reduces proliferation, interferes DNA replication and cell cycle and enhances apoptosis in vascular smooth muscle cells

Abstract

This study examined the effect of artesunate (Art) on the proliferation, DNA replication, cell cycles ans apoptosis of vascular smooth muscle cells (VSMCs). Primary cultures of VSMCs were established from aortas of mice and artesunate of different concentrations was added into the medium. The number of VSMCs was counted and the curve of cell growth was recorded. The activity of VSMCs was assessed by using MTT method and inhibitory rate was calculated. DNA replication was evaluated by [³H]-TdR method and apoptosis by DNA laddering and HE staining. Flowmetry was used for simultaneous analysis of cell apoptosis and cell cycles. Compared with the control group, VSMCs proliferation in Art interfering groups were inhibited and [³H]-TdR incorprating rate were decreased as well as cell apoptosis was induced. The progress of cell cycle was blocked in G₀/G₁ by Art in a dose-dependent manner. It is concluded that Art inhibits VSMCs proliferation by disturbing DNA replication, inducing cell apoptosis and blocking cell cycle in G₀/G₁ phase.

Keywords

proliferation / DNA replication / cell cycle / apoptosis / smooth muscle

References

[1] EpsteinS E, SpeirE, UngerE F, et al. . The basis of molecular strategies for treating coronary Arttenosis after angioplasty. Am Coll Cardiol, 1994, 231278-1278

[2] ChaoZ D, ShiC R, HuangC B. The effect of arterioscler on the proliferation of fibroblastsin vitro. Chongqing Med J (Chinese), 2003, 32(5): 521-521

[3] HaoH, GabbianiG, Bochaton-PiallatM L. Arterial smooth muscle cell heterogeneity: implications for atherosclerosis and Arttenosis development. Arterioscler Thromb Vasc Biol, 2003, 231510-1510

[4] LiuX. The progress in artemisinin research. Guangxi Med J (Chinese), 2003, 25(10): 1950-1950

[5] LouX E. The progress of artesunate in pharmacology and toxicology research. Chin J Hosp Pharm, 2002, 22(3): 175-175

[6] FumarolaC, GuidottiG G. Stress-induced poptosis: toward a symmetry with receptor-mediated cell death. Apoptosis, 2004, 977-77

[7] FergusonJ E, PattersonC. Break the cycle: the role of cell-cycle modulation in the prevention of vasculoproliferative diseases. Cell Cycle, 2003, 2211-211