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Molecules. 2009 Mar 27;14(4):1342-52. doi: 10.3390/molecules14041342.

Evodiamine stabilizes topoisomerase I-DNA cleavable complex to inhibit topoisomerase I activity.

Author information

1
Pharmacy Department, Chi Mei Medical Center, Tainan 710, Taiwan. cmh5500@mail.chimei.org.tw

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 microM 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 microM. The results suggest that EVO inhibits TopI by stabilizing the enzyme and DNA covalent complex.

PMID:
19384267
PMCID:
PMC6254212
DOI:
10.3390/molecules14041342
[Indexed for MEDLINE]
Free PMC Article

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