Evodiamine Stabilizes Topoisomerase I-DNA Cleavable Complex to Inhibit Topoisomerase I Activity

• Main Authors: Jau-Lang Hwang, Chiao-En Chen, Chun-Mao Lin, Chi-Ming Lee, Agnes L.-F. Chan, Wen-Shin Chang, Li-Min Chen
• Format: Article
• Language: English
• Published: MDPI AG 2009-03-01
• Series: Molecules
• Subjects: Evodiamine; Topoisomerase; Covalent complex
• Online Access: http://www.mdpi.com/1420-3049/14/4/1342/

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 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.