G1 phase arrest of the cell cycle by a ginseng metabolite, compound K, in U937 human monocytic leukamia cells
G1 phase arrest of the cell cycle by a ginseng metabolite, compound K, in U937 human monocytic leukamia cells
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DOI：
10.1007/bf02969359
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发表时间：
2005-06-01
影响因子：
6.7
通讯作者：
Hyun, JW
中科院分区：
文献类型：
--
作者：
Kang, KA;Kim, YW;Hyun, JW
我们最近报道了人参皂苷代谢物，化合物K （20- o - β -d -glucopyranosyl-20(S)-protopanaxadiol, IH901）通过caspase依赖性凋亡途径抑制U937细胞的生长。在本研究中，我们进一步表征了化合物K对U937细胞的作用，发现化合物K除了诱导细胞凋亡外，还能诱导G期阻滞。化合物K处理U937细胞后，p21表达增加；一种细胞周期蛋白-cdk复合物的抑制蛋白。p21表达上调后，细胞周期蛋白D和cdk4蛋白失活，细胞周期蛋白E失活，细胞周期蛋白D和cdk4蛋白在G期早期起作用，细胞周期蛋白E在G期晚期起作用。此外，化合物K诱导JNK和转录因子AP-1的激活，AP-1是JNK的下游靶点。这些发现表明，在化合物K处理的细胞中，p21的上调和JNK的激活有助于G(1)期的阻滞。
We recently reported that the ginseng saponin metabolite, compound K (20-O-beta-D-glucopyranosyl-20(S)-protopanaxadiol, IH901), inhibits the growth of U937 cells through caspase-dependent apoptosis pathway. In this study, we further characterized the effects of compound K on U937 cells and found that, in addition to apoptosis, compound K induced the arrest of the G, phase. The compound K treated U937 cells showed increased p21 expression; an inhibitory protein of cyclin-cdk complex. The up-regulation of p21 was followed by the inactivation of cyclin D and the cdk4 protein, which act at the early G, phase, and cyclin E, which acts at the late G, phase. Furthermore, compound K induced the activation of JNK and the transcription factor AP-1, which is a downstream target of JNK. These findings suggest that the up-regulation of p21 and activation of JNK in the compound K treated cells contribute to the arrest of the G(1) phase.