The effects of wedelolactone on cancer cells depend on its redox state

BENEŠ, Petr, Petra ALEXOVA, Lucia KNOPFOVÁ and Jan ŠMARDA. The effects of wedelolactone on cancer cells depend on its redox state. In 19th euroconference on apoptosis, Stocholm, Sweden, 14-17.9, 2011. 2011.

Basic information

• Original name: The effects of wedelolactone on cancer cells depend on its redox state
• Authors: BENEŠ, Petr (203 Czech Republic), Petra ALEXOVA (203 Czech Republic, belonging to the institution), Lucia KNOPFOVÁ (203 Czech Republic) and Jan ŠMARDA (203 Czech Republic, guarantor, belonging to the institution).
• Edition: 19th euroconference on apoptosis, Stocholm, Sweden, 14-17.9, 2011, 2011.

Other information

• Original language: English
• Type of outcome: Conference abstract
• Field of Study: Genetics and molecular biology
• Country of publisher: Sweden
• Confidentiality degree: is not subject to a state or trade secret
• RIV identification code: RIV/00216224:14310/11:00049466
• Organization unit: Faculty of Science
• Keywords in English: wedelolactone; topoisomerase IIa; breast cancer

Abstract

The aim of this study was to further characterize the mechanism how wedelolactone affects topoisomerase IIa and cancer cells. Using electrophoretic mobility shift assay we found that wedelolactone inhibited binding of topoisomerase IIa to supercoiled plasmid DNA. The inhibitory effect of wedelolactone on the topoisomerase IIa was reversed by excess of enzyme but not DNA suggesting that wedelolactone exerted its inhibitory effect by interaction with the topoisomerase II protein. The in vitro inhibitory effect of wedelolactone on the topoisomerase IIa activity was redox-dependent as it diminished in the presence of reducing agents, such as DTT, glutathione, N-acetylcysteine and L-ascorbic acid. Similarly, cytotoxicity of wedelolactone in breast cancer MDA-MB-231 cells was inhibited by N-acetylcysteine but enhanced by buthionine sulfoximine, an inhibitor of glutathione synthesis. Finally, we found that wedelolactone can be oxidized in the presence of copper ions to semiquinone/quinone radicals.

Links

• GA301/09/1115, research and development project: Name: Úloha proteinů c-Myb a Cox-2 při tvorbě střevních nádorů

Investor: Czech Science Foundation, The role of c-Myb and Cox-2 proteins in colon carcinogenesis

• GD204/08/H054, research and development project: Name: Molekulární mechanismy proliferace a diferenciace buněk

Investor: Czech Science Foundation, Molecular mechanisms of the cell proliferation and differentiation

• IAA501630801, research and development project: Name: Mechanismus účinku prokatepsinu D na buňky rakoviny prsu

Investor: Academy of Sciences of the Czech Republic, Mechanism of procathepsin D effect on breast cancer cells

• MSM0021622415, plan (intention): Name: Molekulární podstata buněčných a tkáňových regulací

Investor: Ministry of Education, Youth and Sports of the CR, Molecular basis of cell and tissue regulations