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Inhibition of topoisomerase IIα: novel function of wedelolactone
Petr Benes, Lucia Knopfova, Filip Trcka, Alice Nemajerova, Diana Pinheiro, Karel Soucek, Miroslav Fojta, Jan Smarda
Language English Country Ireland
Document type Journal Article, Research Support, Non-U.S. Gov't
Grant support
NS9600
MZ0
CEP Register
- MeSH
- Antigens, Neoplasm metabolism MeSH
- Apoptosis drug effects MeSH
- Cell Cycle drug effects MeSH
- Cell Growth Processes drug effects MeSH
- DNA-Binding Proteins antagonists & inhibitors metabolism MeSH
- DNA Topoisomerases, Type II metabolism MeSH
- Enzyme-Linked Immunosorbent Assay MeSH
- Immunoblotting MeSH
- Topoisomerase Inhibitors pharmacology MeSH
- Coumarins pharmacology MeSH
- Humans MeSH
- Cell Line, Tumor MeSH
- Breast Neoplasms drug therapy enzymology pathology MeSH
- DNA Damage MeSH
- Antineoplastic Agents pharmacology MeSH
- Signal Transduction MeSH
- Cell Survival drug effects MeSH
- Check Tag
- Humans MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
The naturally occurring coumestan wedelolactone has been previously shown to reduce growth of various cancer cells. So far, the growth-suppressing effect of wedelolactone has been attributed to the inhibition of the NFκB transcription factor and/or androgen receptors. We found that wedelolactone suppressed growth and induced apoptosis of androgen receptor-negative MDA-MB-231 breast cancer cells at concentrations that did not inhibit the NFκB activity. The cells responded to wedelolactone by the S and G2/M phase cell cycle arrest and induction of the DNA damage signaling. Wedelolactone interacted with dsDNA and inhibited the activity of DNA topoisomerase IIα. We conclude that wedelolactone can act as growth suppressor independently of NFκB and androgen receptors.
References provided by Crossref.org
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- $a The naturally occurring coumestan wedelolactone has been previously shown to reduce growth of various cancer cells. So far, the growth-suppressing effect of wedelolactone has been attributed to the inhibition of the NFκB transcription factor and/or androgen receptors. We found that wedelolactone suppressed growth and induced apoptosis of androgen receptor-negative MDA-MB-231 breast cancer cells at concentrations that did not inhibit the NFκB activity. The cells responded to wedelolactone by the S and G2/M phase cell cycle arrest and induction of the DNA damage signaling. Wedelolactone interacted with dsDNA and inhibited the activity of DNA topoisomerase IIα. We conclude that wedelolactone can act as growth suppressor independently of NFκB and androgen receptors.
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