CK2 inhibition induces apoptosis via the ER stress response
CK2 inhibition induces apoptosis via the ER stress response
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DOI：
10.1016/j.cellsig.2010.08.014
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发表时间：
2011-01-01
影响因子：
4.8
通讯作者：
Montenarh, Mathias
中科院分区：
文献类型：
--
作者：
Hessenauer, Andrea;Schneider, Carolin C.;Montenarh, Mathias
蛋白激酶CK 2是一种普遍表达的丝氨酸/苏氨酸激酶，由两个催化α/α '和两个调节β亚基组成。CK 2的表达在肿瘤细胞中高度升高，其保护细胞免于凋亡。因此，已知CK 2的抑制诱导程序性细胞死亡，使其成为癌症治疗的有希望的靶标。在本研究中，我们研究了CK 2抑制剂4，5，6，7-四溴苯并三唑（TBB）在前列腺肿瘤细胞中的凋亡诱导作用。与PC-3细胞相反，LNCaP细胞响应于CK 2抑制而发生凋亡。最有趣的是，我们发现在LNCaP以及PC-3细胞中诱导的线粒体途径通过下调bcl-2和随后的细胞色素c释放来监测。在这两种细胞系中均未检测到半胱天冬酶9的活化。相反，激活的内质网（ER）应激反应在LNCaP细胞与CK 2抑制剂TBB治疗后被发现。我们表明，这种ER应激反应导致上调死亡受体DR 5和随后的LNCaP细胞凋亡。(C)2010年爱思唯尔公司All rights reserved.
Protein kinase CK2 is a ubiquitously expressed serine/threonine kinase consisting of two catalytic alpha/alpha' and two regulatory beta subunits. Expression of CK2 is highly elevated in tumor cells where it protects cells from apoptosis. Accordingly inhibition of CK2 is known to induce programmed cell death, making it a promising target for cancer therapy. In the present study we investigated apoptosis induction by the CK2 inhibitor 4,5,6,7-tetrabromobenzotriazole (TBB) in prostate tumor cells. In contrast to PC-3 cells LNCaP cells respond to CK2 inhibition with apoptosis. Most interestingly we found the mitochondrial pathway induced in LNCaP as well as in PC-3 cells as monitored by down-regulation of bcl-2 and subsequent cytochrome c release. In both cell lines activation of caspase 9 was not detected. Instead, an activation of the endoplasmic reticulum (ER) stress response in LNCaP cells after treatment with the CK2 inhibitor TBB was found. We show that this ER stress response led to an up-regulation of the death receptor DR5 and subsequent apoptosis in LNCaP cells. (C) 2010 Elsevier Inc. All rights reserved.