title: Evodiamine stabilizes topoisomerase I-DNA cleavable complex to inhibit topoisomerase I activity.
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.
authors.affiliation: Pharmacy Department, Chi Mei Medical Center, Tainan 710, Taiwan. cmh5500@mail.chimei.org.tw
authors.forename: Agnes L-F
authors.initials: AL
authors.lastname: Chan
authors.forename: Wen-Shin
authors.initials: WS
authors.lastname: Chang
authors.forename: Li-Min
authors.initials: LM
authors.lastname: Chen
authors.forename: Chi-Ming
authors.initials: CM
authors.lastname: Lee
authors.forename: Chiao-En
authors.initials: CE
authors.lastname: Chen
authors.forename: Chun-Mao
authors.initials: CM
authors.lastname: Lin
authors.forename: Jau-Lang
authors.initials: JL
authors.lastname: Hwang
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism; D045744:Cell Line, Tumor; D004264:DNA Topoisomerases, Type I / Q000378:metabolism; D004278:DNA, Superhelical / Q000378:metabolism*; D004795:Enzyme Stability; D005260:Female; D006801:Humans; D046911:Macromolecular Substances / Q000378:metabolism*; D015394:Molecular Structure; D010936:Plant Extracts / Q000737:chemistry / Q000378:metabolism*; D011799:Quinazolines / Q000737:chemistry / Q000378:metabolism*; D059004:Topoisomerase I Inhibitors
chemical_list: D004278:DNA, Superhelical; D046911:Macromolecular Substances; D010936:Plant Extracts; D011799:Quinazolines; D059004:Topoisomerase I Inhibitors; C049639:evodiamine; D004264:DNA Topoisomerases, Type I