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Molecules 2009, 14(4), 1342-1352; doi:10.3390/molecules14041342

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

1
Pharmacy Department, Chi Mei Medical Center, Tainan 710, Taiwan
2
College of Pharmacy, Taipei Medical University, Taipei 110, Taiwan
3
College of Medicine, Taipei Medical University, Taipei 110, Taiwan
4
Institute of Molecular Biology, Academia Sinica, Nangkang, Taipei 115, Taiwan
5
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 / Revised: 13 March 2009 / Accepted: 18 March 2009 / Published: 27 March 2009
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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 Evodiamine; Topoisomerase; Covalent complex
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MDPI and ACS Style

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.

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