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[摘要]：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. |
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