title: Induction of apoptosis by evodiamine involves both activation of mitotic             arrest and mitotic slippage.
abstract: 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.
authors: Department of Pathophysiology, Medical College of Jinan University, and Department of Neurology, First Affiliated Hospital of Jinan University, Guangzhou 510632, PR China.
authors: Li-Hong
authors: LH
authors: Zhu
authors: Wei
authors: W
authors: Bi
authors: Xiao-Dong
authors: XD
authors: Liu
authors: Jie-Fen
authors: JF
authors: Li
authors: Ying-Ya
authors: YY
authors: Wu
authors: Biao-Yan
authors: BY
authors: Du
authors: Yu-Hui
authors: YH
authors: Tan
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D056744:Cyclin B1 / Q000235:genetics / Q000378:metabolism; D019927:Cyclin E / Q000235:genetics / Q000378:metabolism; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D008938:Mitosis / Q000187:drug effects*; D011799:Quinazolines / Q000494:pharmacology*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; C534699:CCNB1 protein, human; D056744:Cyclin B1; D019927:Cyclin E; D011799:Quinazolines; C049639:evodiamine