Evodiamine stabilizes topoisomerase I-DNA cleavable complex to inhibit topoisomerase I activity.
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.
Chan
Agnes L-F
AL
Pharmacy Department, Chi Mei Medical Center, Tainan 710, Taiwan. cmh5500@mail.chimei.org.tw
Chang
Wen-Shin
WS
Chen
Li-Min
LM
Lee
Chi-Ming
CM
Chen
Chiao-En
CE
Lin
Chun-Mao
CM
Hwang
Jau-Lang
JL
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
D004278:DNA, Superhelical; D046911:Macromolecular Substances; D010936:Plant Extracts; D011799:Quinazolines; D059004:Topoisomerase I Inhibitors; C049639:evodiamine; D004264:DNA Topoisomerases, Type I