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

Agnes L F Chan, Wen Shin Chang, Li Min Chen, Chi Ming Lee, Chiao En Chen, Chun Mao Lin, Jau Lang Hwang

Research output: Contribution to journalArticlepeer-review

33 Citations (Scopus)

Abstract

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 0̃10 μM 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 μM. The results suggest that EVO inhibits TopI by stabilizing the enzyme and DNA covalent complex.

Original languageEnglish
Pages (from-to)1342-1352
Number of pages11
JournalMolecules
Volume14
Issue number4
DOIs
Publication statusPublished - Apr 2009

Keywords

  • Covalent complex
  • Evodiamine
  • Topoisomerase

ASJC Scopus subject areas

  • Analytical Chemistry
  • Chemistry (miscellaneous)
  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery
  • Physical and Theoretical Chemistry
  • Organic Chemistry

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