Evodiamine Stabilizes Topoisomerase I-DNA Cleavable Complex to Inhibit Topoisomerase I Activity
| Autor: | Chiao En Chen, Agnes L F Chan, Li Min Chen, Chi Ming Lee, Chun Mao Lin, Wen Shin Chang, Jau Lang Hwang |
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| Rok vydání: | 2009 |
| Předmět: |
Evodiamine
Macromolecular Substances medicine.drug_class Pharmaceutical Science Breast Neoplasms Topoisomerase-I Inhibitor Article Analytical Chemistry lcsh:QD241-441 chemistry.chemical_compound lcsh:Organic chemistry Cell Line Tumor Enzyme Stability Drug Discovery medicine Animals Humans Physical and Theoretical Chemistry Covalent complex chemistry.chemical_classification Topoisomerase Molecular Structure biology DNA Superhelical Plant Extracts Organic Chemistry Molecular biology Enzyme DNA Topoisomerases Type I chemistry Chemistry (miscellaneous) Cell culture Covalent bond Quinazolines biology.protein Molecular Medicine Female Topoisomerase I Inhibitors Topoisomerase inhibitor DNA |
| Zdroj: | Molecules; Volume 14; Issue 4; Pages: 1342-1352 Molecules, Vol 14, Iss 4, Pp 1342-1352 (2009) Molecules |
| ISSN: | 1420-3049 |
| DOI: | 10.3390/molecules14041342 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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