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 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.
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Chan, A.L.-F.; Chang, W.-S.; Chen, L.-M.; Lee, C.-M.; Chen, C.-E.; Lin, C.-M.; Hwang, J.-L. Evodiamine Stabilizes Topoisomerase I-DNA Cleavable Complex to Inhibit Topoisomerase I Activity. Molecules 2009, 14, 1342-1352.
Chan AL-F, Chang W-S, Chen L-M, Lee C-M, Chen C-E, Lin C-M, Hwang J-L. Evodiamine Stabilizes Topoisomerase I-DNA Cleavable Complex to Inhibit Topoisomerase I Activity. Molecules. 2009; 14(4):1342-1352.
Chan, Agnes L.-F.; Chang, Wen-Shin; Chen, Li-Min; Lee, Chi-Ming; Chen, Chiao-En; Lin, Chun-Mao; Hwang, Jau-Lang. 2009. "Evodiamine Stabilizes Topoisomerase I-DNA Cleavable Complex to Inhibit Topoisomerase I Activity." Molecules 14, no. 4: 1342-1352.