| BENEŠ, Petr, Petra ALEXOVA, Lucia KNOPFOVÁ, Alena ŠPANOVÁ a Jan ŠMARDA. Redox State Alters Anti-Cancer Effects of Wedelolactone. Environmental and Molecular Mutagenesis. Wiley Periodicals Inc., 2012, roč. 53, č. 7, s. 515-524. ISSN 0893-6692. Dostupné z: https://dx.doi.org/10.1002/em.21712. |
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@article{989183,
author = {Beneš, Petr and Alexova, Petra and Knopfová, Lucia and Španová, Alena and Šmarda, Jan},
article_number = {7},
doi = {http://dx.doi.org/10.1002/em.21712},
keywords = {cell death; DNA damage; topoisomerase; wedelolactone},
language = {eng},
issn = {0893-6692},
journal = {Environmental and Molecular Mutagenesis},
title = {Redox State Alters Anti-Cancer Effects of Wedelolactone},
volume = {53},
year = {2012}
}
TY - JOUR
ID - 989183
AU - Beneš, Petr - Alexova, Petra - Knopfová, Lucia - Španová, Alena - Šmarda, Jan
PY - 2012
TI - Redox State Alters Anti-Cancer Effects of Wedelolactone
JF - Environmental and Molecular Mutagenesis
VL - 53
IS - 7
SP - 515-524
EP - 515-524
PB - Wiley Periodicals Inc.
SN - 08936692
KW - cell death
KW - DNA damage
KW - topoisomerase
KW - wedelolactone
N2 - Wedelolactone is one of the active plant polyphenolic compounds. Anti-tumor effects of this drug have been demonstrated recently. We have described that wedelolactone acts as catalytic inhibitor of DNA topoisomerase IIa. The aim of this study was to further characterize the mechanism of its anti-tumor effects. We showed that wedelolactone inhibits binding of DNA topoisomerase IIa to plasmid DNA and antagonizes formation of etoposide-induced DNA cleavage complex. The inhibition of topoisomerase IIa by wedelolactone is reversible by excess of the enzyme but not DNA. The in vitro inhibitory effect of wedelolactone on the topoisomerase IIa activity is redox-dependent as it diminished in the presence of reducing agents. Cytotoxicity of wedelolactone was partially inhibited by N-acetylcysteine and glutathione ethyl ester in breast cancer MDA-MB-231 and MDA-MB-468 cells while the inhibitory effect of catalase was observed only in the former cell line. Finally, we found that wedelolactone can be oxidized in the presence of copper ions resulting in DNA strand break and abasic site formation in vitro. However, wedelolactone induced neither DNA damage in MDA-MB-231 cells nor mutations in bacterial cells detectable by Ames test suggesting that wedelolactone may not be an effective inducer of DNA damage. We conclude that the topoisomerase IIa inhibitory- and DNA damaging activities of wedelolactone in vitro depend on its redox state. Pro-oxidant activity could, however, explain only part of wedelolactone-induced cytotoxicity. Therefore, the major cellular target(s) of wedelolactone and the exact mechanism of wedelolactone-induced cytotoxicity still remain to be identified.
ER -
BENEŠ, Petr, Petra ALEXOVA, Lucia KNOPFOVÁ, Alena ŠPANOVÁ a Jan ŠMARDA. Redox State Alters Anti-Cancer Effects of Wedelolactone. \textit{Environmental and Molecular Mutagenesis}. Wiley Periodicals Inc., 2012, roč.~53, č.~7, s.~515-524. ISSN~0893-6692. Dostupné z: https://dx.doi.org/10.1002/em.21712.
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