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Evodiamine Stabilizes Topoisomerase I-DNA Cleavable Complex to Inhibit Topoisomerase I Activity
Pharmacy Department, Chi Mei Medical Center, Tainan 710, Taiwan
College of Pharmacy, Taipei Medical University, Taipei 110, Taiwan
College of Medicine, Taipei Medical University, Taipei 110, Taiwan
Institute of Molecular Biology, Academia Sinica, Nangkang, Taipei 115, Taiwan
Orthopedics Research Center, Taipei Medical University Hospital, Taipei 110, Taiwan
These authors contributed equally to this work
* Authors to whom correspondence should be addressed.
Received: 21 February 2009; in revised form: 13 March 2009 / Accepted: 18 March 2009 / Published: 27 March 2009
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.
Keywords: Evodiamine; Topoisomerase; 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.