Oridonin induces G2/M arrest and apoptosis via activating ERK-p53 apoptotic pathway and inhibiting PTK-Ras-Raf-JNK survival pathway in murine fibrosarcoma L929 cells
Oridonin induces G2/M arrest and apoptosis via activating ERK-p53 apoptotic pathway and inhibiting PTK-Ras-Raf-JNK survival pathway in murine fibrosarcoma L929 cells
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DOI：
10.1016/j.abb.2009.08.011
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发表时间：
2009-10-01
影响因子：
3.9
通讯作者：
Ikejima, Takashi
中科院分区：
文献类型：
--
作者：
Cheng, Yan;Qiu, Feng;Ikejima, Takashi
冬凌草甲素可通过ROS介导的线粒体和ERK途径诱导L929细胞凋亡，但具体机制尚不清楚。本文所我们发现，冬凌草甲素处理诱导G2/M期细胞百分比增加。G2/M期阻滞与细胞周期相关的cdc 2、cdc 25 c和cycling水平下调以及p21和p-cdc 2水平上调有关。此外，我们发现阻断p53的激活可以减少冬凌草甲素诱导的细胞凋亡，通过特异性抑制剂或siRNA阻断ERK可以抑制冬凌草甲素诱导的p53激活。此外，抑制PTK、蛋白激酶C。Ras、Raf或JNK的激活增加了冬凌草甲素诱导的细胞凋亡。冬凌草甲素可下调Ras、Raf和JNK的表达，抑制PTK、Ras、Raf的活化可降低p-JNK的表达。结论：冬凌草甲素诱导L929细胞G2/M期阻滞和凋亡，其机制可能与促进ERK-p53凋亡通路和抑制PFK介导的生存通路有关。(C)2009 Elsevier Inc. All rights reserved.
Oridonin was reported to induce L929 cell apoptosis via ROS-mediated mitochondrial and ERK pathways: however, the precise mechanisms by which oridonin induces cell death remain unclear. Herein. we found that oridonin treatment induced an increase in G(2)/M phase cell percentage. And, G(2)/M phase arrest was associated with down-regulation of cell cycle related cdc2, cdc25c and cycling levels, as well as up-regulation of p21 and p-cdc2 levels. In addition, we discovered that interruption of p53 activation decreased oridonin-induced apoptosis, and blocking ERK by specific inhibitors or siRNA suppressed oridonin-induced p53 activation. Moreover, inhibition of PTK, protein kinase C. Ras, Raf or JNK activation increased oridonin-induced apoptosis. Also, the level of Ras, Raf or JNK was down-regulated by oridonin, and the inhibition of PTK, Ras, Raf activation decreased p-JNK level. In conclusion, oridonin induces L929 cell G(2)/M arrest and apoptosis, which is regulated by promoting ERK-p53 apoptotic pathway and suppressing PFK-mediated survival pathway. (C) 2009 Elsevier Inc. All rights reserved.