Evodiamine stabilizes topoisomerase I-DNA cleavable complex to inhibit topoisomerase I activity

Molecules. 2009 Mar 27;14(4):1342-52. doi: 10.3390/molecules14041342.


Evodiamine (EVO), an alkaloidal compound isolated from Evodia rutaecarpa (Juss.), has been reported to affect many physiological functions. Topoisomerase inhibitors have been developed in a variety of clinical applications. In the present study, we report the topoisomerase I (TopI) inhibitory activity of EVO, which may have properties that lead to improved therapeutic benefits. EVO is able to inhibit supercoiled plasmid DNA relaxation catalyzed by TopI. Upon treatment 0-10 microM EVO TopI was depleted in MCF-7 breast cancer cells in a concentration-dependent and time-dependent manner in 0-120 min. A K-SDS precipitation assay was performed to measure the extent of Top I-trapped chromosomal DNA. The ability of EVO to cause the formation of a TopI-DNA complex increased in a concentration-dependent manner, in that the DNA trapped increased by 24.2% in cells treated with 30 microM. The results suggest that EVO inhibits TopI by stabilizing the enzyme and DNA covalent complex.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Breast Neoplasms / metabolism
  • Cell Line, Tumor
  • DNA Topoisomerases, Type I / metabolism
  • DNA, Superhelical / metabolism*
  • Enzyme Stability
  • Female
  • Humans
  • Macromolecular Substances / metabolism*
  • Molecular Structure
  • Plant Extracts / chemistry
  • Plant Extracts / metabolism*
  • Quinazolines / chemistry
  • Quinazolines / metabolism*
  • Topoisomerase I Inhibitors*


  • DNA, Superhelical
  • Macromolecular Substances
  • Plant Extracts
  • Quinazolines
  • Topoisomerase I Inhibitors
  • evodiamine
  • DNA Topoisomerases, Type I