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

被引：47

作者：

Chan, Agnes L. -F. ^{[2
]}

Chang, Wen-Shin ^{[3
]}

Chen, Li-Min ^{[1
]}

Lee, Chi-Ming ^{[1
]}

Chen, Chiao-En ^{[4
]}

Lin, Chun-Mao ^{[1
,5
]}

Hwang, Jau-Lang ^{[4
]}

机构：

[1] Taipei Med Univ, Coll Med, Taipei 110, Taiwan

[2] Chi Mei Med Ctr, Dept Pharm, Tainan 710, Taiwan

[3] Taipei Med Univ, Coll Pharm, Taipei 110, Taiwan

[4] Acad Sinica, Inst Mol Biol, Taipei 115, Taiwan

[5] Taipei Med Univ Hosp, Orthoped Res Ctr, Taipei 110, Taiwan

来源：

MOLECULES | 2009年 / 14卷 / 04期

关键词：

Evodiamine; Topoisomerase; Covalent complex; CELLS; CAMPTOTHECIN; INVOLVEMENT; MECHANISMS; CARCINOMA; FRUCTUS; VITRO;

D O I：

10.3390/molecules14041342

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 similar to 10 mu M EVO TopI was depleted in MCF-7 breast cancer cells in a concentration-dependent and time-dependent manner in 0 similar to 120 min. A K-SDS precipitation assay was performed to measure the extent of Top I-trappedchromosomal 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 mu M. The results suggest that EVO inhibits TopI by stabilizing the enzyme and DNA covalent complex.

引用

页码：1342 / 1352

页数：11

共 28 条

[1] Type II topoisomerases as targets for quinolone antibacterials: turning Dr. Jekyll into Mr. Hyde [J].