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• Chan, AL.-F.
• Chang, W
• Chen, L
• Lee, C
• Chen, C
• Lin, C
• Hwang, J
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• Chan, AL.-F.
• Chang, W
• Chen, L
• Lee, C
• Chen, C
• Lin, C
• Hwang, J
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• Chan, AL.-F.
• Chang, W
• Chen, L
• Lee, C
• Chen, C
• Lin, C
• Hwang, J

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

Article

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

Agnes L.-F. Chan ¹ , Wen-Shin Chang ² , Li-Min Chen ³ , Chi-Ming Lee ³ , Chiao-En Chen ⁴ , Chun-Mao Lin ^{3, 5, †,}*  and Jau-Lang Hwang ^{4, †,}*

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; in revised form: 13 March 2009 / Accepted: 18 March 2009 / Published: 27 March 2009

Download PDF Full-Text [248 KB, uploaded 27 March 2009 10:57 CET]

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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