Induction of apoptosis by evodiamine involves both activation of mitotic arrest and mitotic slippage

Oncol Rep. 2011 Dec;26(6):1447-55. doi: 10.3892/or.2011.1444. Epub 2011 Sep 1.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Apoptosis / drug effects*
  • Cell Culture Techniques
  • Cell Line, Tumor
  • Cyclin B1 / genetics
  • Cyclin B1 / metabolism
  • Cyclin E / genetics
  • Cyclin E / metabolism
  • G2 Phase Cell Cycle Checkpoints / drug effects*
  • Gene Expression / drug effects
  • Humans
  • Mitosis / drug effects*
  • Quinazolines / pharmacology*


  • Antineoplastic Agents, Phytogenic
  • CCNB1 protein, human
  • Cyclin B1
  • Cyclin E
  • Quinazolines
  • evodiamine