Inhibition of topoisomerase IIα: Novel function of wedelolactone
Inhibition of topoisomerase IIα: Novel function of wedelolactone
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DOI：
10.1016/j.canlet.2011.01.002
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发表时间：
2011-04-01
期刊：
影响因子：
9.7
通讯作者：
Smarda, Jan
中科院分区：
文献类型：
--
作者：
Benes, Petr;Knopfova, Lucia;Smarda, Jan
天然存在的香豆藤酮先前已被证明可以减少各种癌细胞的生长。迄今为止，已将wedelolactone的生长抑制作用归因于NF κ B转录因子和/或雄激素受体的抑制。我们发现，在不抑制NF κ B活性的浓度下，wedelolactone可抑制雄激素受体阴性MDA-MB-231乳腺癌细胞的生长并诱导其凋亡。结果表明，雷公藤内酯醇可使细胞周期阻滞于S期和G2/M期，并诱导DNA损伤信号。Wedelolactone与dsDNA相互作用并抑制DNA拓扑异构酶II α的活性。我们的结论是，wedelolactone可以作为独立的NF κ B B和雄激素受体的生长抑制剂。(C)2011爱思唯尔爱尔兰有限公司保留所有权利。
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 NF kappa B 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 NF kappa B 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 II alpha. We conclude that wedelolactone can act as growth suppressor independently of NF kappa B and androgen receptors. (C) 2011 Elsevier Ireland Ltd. All rights reserved.