Induction of apoptosis by evodiamine involves both activation of mitotic arrest and mitotic slippage.
Induction of apoptosis by evodiamine involves both activation of mitotic arrest and mitotic slippage.
复制标题
DOI：
10.3892/or.2011.1444
复制
发表时间：
2011-12
期刊：
影响因子：
4.2
通讯作者：
Lihong Zhu;Wei Bi;Xiao-Dong Liu;Jieyun Li;Ying-ya Wu;B. Du;Yuhui Tan
中科院分区：
文献类型：
--
作者：
Lihong Zhu;Wei Bi;Xiao-Dong Liu;Jieyun Li;Ying-ya Wu;B. Du;Yuhui Tan
evolodiamine （Evo）是一种从吴茱萸果实中分离得到的吲哚喹唑啉类生物碱。先前的研究表明，Evo在几种癌症类型中具有抗增殖抗肿瘤活性，但其作用靶点和潜在机制尚不清楚。在本研究中，我们试图建立细胞同步模型，以研究Evo在人胃癌细胞系SGC-7901中的抗增殖和凋亡机制。此外，我们用全长或不可降解（ND） cyclinB1转染这些细胞，以评估Evo诱导凋亡与激活有丝分裂停止和有丝分裂滑移之间的关系。我们的研究结果表明，Evo显著抑制细胞生长，并对SGC-7901细胞具有细胞毒性。此外，短暂的Evo处理（<16 h）引起可逆的有丝分裂停止，但持续的有丝分裂停止需要启动细胞凋亡。逆转Evo的凋亡作用所需的时间在16到20小时之间。我们还证明了CDK1抑制剂促进有丝分裂滑移可增强细胞凋亡。此外，我们还通过过表达ND cyclinB1来延缓细胞凋亡，从而评估其延缓有丝分裂滑移的作用。总之，这些结果表明Evo诱导的细胞凋亡与有丝分裂停止和随后的有丝分裂滑脱有关，这可能是Evo在治疗和预防癌症中的作用的基础。
Evodiamine (Evo) is an indole quinazoline alkaloid isolated from the fruit of Evodia rutaecarpa Bentham. Previous studies have shown that Evo exhibits anti-proliferative anti-tumor activities in several cancer types, but its target(s) and underlying mechanism(s) of action remain unclear. In the present study, we sought to establish a cell synchronization model in order to examine the anti-proliferative and apoptotic mechanisms of Evo in the human gastric cancer cell line SGC-7901. In addition, we transfected these cells with full-length or non-degradable (ND) cyclinB1 to evaluate the relationship between the induction of apoptosis and activation of mitotic arrest and mitotic slippage by Evo. Our results demonstrated that Evo markedly inhibited cell growth and was cytotoxic to SGC-7901 cells. Furthermore, transient Evo treatment (<16 h) caused reversible mitotic arrest, but sustained mitotic arrest was required to initiate apoptosis. The time required to reverse the apoptotic effects of Evo was between 16 and 20 h. We also demonstrated that promotion of mitotic slippage by a CDK1 inhibitor enhanced apoptosis. Furthermore, we evaluated the effect of delaying mitotic slippage by overexpressing ND cyclinB1, which delayed apoptosis. In conclusion, these results indicate that Evo-induced apoptosis is associated with mitotic arrest and subsequent mitotic slippage, which may underlie the actions of Evo in the treatment and prevention of cancer.