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

Agnes L F Chan; Wen Shin Chang; Li Min Chen; Chi Ming Lee; Chiao En Chen; Chun Mao Lin; Jau Lang Hwang

doi:10.3390/molecules14041342

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

Agnes L F Chan, Wen Shin Chang, Li Min Chen, Chi Ming Lee, Chiao En Chen, Chun Mao Lin, Jau Lang Hwang

Department of Biochemistry and Molecular Cell Biology

Research output: Contribution to journal › Article › peer-review

47 Citations (Scopus)

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 0̃10 μM 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 μM. The results suggest that EVO inhibits TopI by stabilizing the enzyme and DNA covalent complex.

Original language	English
Pages (from-to)	1342-1352
Number of pages	11
Journal	Molecules
Volume	14
Issue number	4
DOIs	https://doi.org/10.3390/molecules14041342
Publication status	Published - Apr 2009

Keywords

Covalent complex
Evodiamine
Topoisomerase

ASJC Scopus subject areas

Analytical Chemistry
Chemistry (miscellaneous)
Molecular Medicine
Pharmaceutical Science
Drug Discovery
Physical and Theoretical Chemistry
Organic Chemistry

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.3390/molecules14041342

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

keywords = "Covalent complex, Evodiamine, Topoisomerase",

author = "Chan, {Agnes L F} and Chang, {Wen Shin} and Chen, {Li Min} and Lee, {Chi Ming} and Chen, {Chiao En} and Lin, {Chun Mao} and Hwang, {Jau Lang}",

year = "2009",

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T1 - Evodiamine stabilizes topoisomerase I-DNA cleavable complex to inhibit topoisomerase I activity

AU - Chan, Agnes L F

AU - Chang, Wen Shin

AU - Chen, Li Min

AU - Lee, Chi Ming

AU - Chen, Chiao En

AU - Lin, Chun Mao

AU - Hwang, Jau Lang

PY - 2009/4

Y1 - 2009/4

N2 - 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 0̃10 μM 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 μM. The results suggest that EVO inhibits TopI by stabilizing the enzyme and DNA covalent complex.

AB - 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 0̃10 μM 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 μM. The results suggest that EVO inhibits TopI by stabilizing the enzyme and DNA covalent complex.

KW - Covalent complex

KW - Evodiamine

KW - Topoisomerase

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

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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