UNBS1450, a steroid cardiac glycoside inducing apoptotic cell death in human leukemia cells
UNBS1450, a steroid cardiac glycoside inducing apoptotic cell death in human leukemia cells
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DOI：
10.1016/j.bcp.2010.08.025
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发表时间：
2011-01-01
影响因子：
5.8
通讯作者：
Diederich, Marc
中科院分区：
文献类型：
--
作者：
Juncker, Tom;Cerella, Claudia;Diederich, Marc
心脏类固醇用于治疗各种疾病，包括充血性心力衰竭和癌症。本研究的目的是研究UNBS1450的抗白血病活性，UNBS1450是一种半合成的cardenolide，属于心脏类固醇糖苷家族。在这里，我们报道，在低纳摩尔浓度下，UNBS1450诱导凋亡细胞死亡。随后，我们研究了导致细胞凋亡激活的分子机制。我们的研究结果表明，UNBS1450抑制NF-kappa B的反激活，并通过切割前caspases 8、9和3/7，降低抗凋亡Mcl-1的表达，以及募集促凋亡的Bak和Bax蛋白，最终导致细胞死亡，从而引发细胞凋亡。(C) 2010爱思唯尔公司版权所有。
Cardiac steroids are used to treat various diseases including congestive heart failure and cancer. The aim of this study was to investigate the anti-leukemic activity of UNBS1450, a hemi-synthetic cardenolide belonging to the cardiac steroid glycoside family. Here, we report that, at low nanomolar concentrations, UNBS1450 induces apoptotic cell death. Subsequently, we have investigated the molecular mechanisms leading to apoptosis activation. Our results show that UNBS1450 inhibits NF-kappa B transactivation and triggers apoptosis by cleavage of pro-caspases 8, 9 and 3/7, by decreasing expression of anti-apoptotic Mcl-1 and by recruitment of pro-apoptotic Bak and Bax protein eventually resulting in cell death. (C) 2010 Elsevier Inc. All rights reserved.