Ginsenoside-Rh2 blocks the cell cycle of SK-HEP-1 cells at the G1/S boundary by selectively inducing the protein expression of p27(kip1)

Ginsenoside-Rh2 blocks the cell cycle of SK-HEP-1 cells at the G1/S boundary by selectively inducing the protein expression of p27(kip1)
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DOI:
10.1016/s0304-3835(96)04502-8
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发表时间:
1996-12-20
期刊:
影响因子:
9.7
通讯作者:
Lee, SK
Lee, SK
中科院分区:
医学1区
文献类型:
--
作者:
Lee, KY;Park, JA;Lee, SK

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本文报道了人参皂甙Rh_2(G-Rh_2)抑制SK-HEP-1细胞增殖的作用机制。流式细胞术结果表明,G-Rh_2使细胞周期阻滞于G_1/S期。细胞周期蛋白E依赖性激酶的活性,已免疫沉淀细胞周期蛋白E特异性抗体下调的细胞响应于G-Rh 2。将激酶活性下调50%所需的IC 50值约为0.75 μ M。免疫印迹分析表明,G-Rh 2以剂量依赖性方式选择性诱导p27(kip 1)的表达,而对细胞周期蛋白E、cdk 2和p21(WAF 1)的水平没有影响。此外,我们的数据表明,G-Rh 2在剂量高于10 μ M时降低cdc 25 A的蛋白水平。总的来说,这些数据表明,红景天苷-Rh 2通过选择性诱导p27(Kip 1)的蛋白表达,并因此下调细胞周期蛋白E依赖性激酶活性,将细胞周期阻滞在G1/S过渡期。
The mechanism of action by which ginsenoside-Rh2 (G-Rh2) suppresses the proliferation of SK-HEP-1 cells is reported, The results from flow cytometric analyses show that G-Rh2 arrested the cell cycle at the G1/S transition phase. The cyclin E-dependent kinase activity which had been immunoprecipitated with cyclin E-specific antibody was down-regulated in the cells in response to G-Rh2. The IC50 value required to down-regulate the kinase activity by 50% was approximately 0.75 mu M. Immunoblotting analyses show that G-Rh2 selectively induced the expression of p27(kip1) in a dose-dependent manner whereas it had no effect on the levels of cyclin E, cdk2, and p21(WAF1). In addition, our data show that G-Rh2 reduced the protein levels of cdc25A at doses higher than 10 mu M. Collectively, these data suggest that ginsenoside-Rh2 arrests the cell cycle at the G1/S transition phase by selectively inducing protein expression of p27(Kip1) and, as a consequence, down-regulating cyclin E-dependent kinase activity.