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

• Autoři: BENEŠ Petr; ALEXOVA Petra; KNOPFOVÁ Lucia; ŠMARDA Jan
• Rok publikování: 2011
• Druh: Konferenční abstrakty
• Fakulta / Pracoviště MU: Přírodovědecká fakulta
• Popis: 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.

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