Protein kinase CK2 plays multiple roles in cell function in normal and disease states. CK2 is elevated in numerous types of cancer cells, and CK2 suppression of apoptosis represents a key link to the cancer cell phenotype. CK2 regulation of cell survival and death involves diverse processes, and our previous work suggested that mitochondrial machinery is a key locus of this function. One of the earliest responses of prostate cells to inhibition of CK2 is a change in mitochondrial membrane potential, possibly associated with Ca2+ signaling. Thus, in the present work, we investigated early impact of CK2 on intracellular Ca2+ dynamics. Three prostate cancer (PCa) cell lines, PC3-LN4, C4-2B, and 22Rv1, were studied. PCa cells were treated with the CK2 small molecule inhibitors 4,5,6,7-tetrabrombenzotriazole and CX-4945 followed by analysis of Ca2+ levels in various cellular compartments over time. The results showed dose-dependent loss in cytosolic Ca2+ levels starting within 2 min and reaching maximal loss within 5-10 min. There was a concomitant increase in Ca2+ in the endoplasmic reticulum (ER) and mitochondrial compartments. The results suggest that inhibition of CK2 activity results in a rapid movement of Ca2+ out of the cytosol and into the ER and mitochondria, which may be among the earliest contributory factors for induction of apoptosis in cells subjected to inhibition of CK2. In cells with death-inducing levels of CK2 inhibition, total cellular Ca2+ levels dropped at 2 h post-treatment. These novel observations represent a potential mechanism underlying regulation of cell survival and death by CK2 activity.

中文翻译：

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蛋白激酶CK2对前列腺癌细胞内钙稳态的影响。

蛋白激酶CK2在正常和疾病状态下在细胞功能中发挥多种作用。CK2在多种类型的癌细胞中升高，而CK2抑制凋亡代表了与癌细胞表型的关键联系。CK2对细胞存活和死亡的调控涉及多个过程，而我们先前的工作表明线粒体机制是该功能的关键基因座。前列腺细胞对CK2抑制的最早反应之一是线粒体膜电位的变化，可能与Ca2 +信号传导有关。因此，在目前的工作中，我们调查了CK2对细胞内Ca2 +动力学的早期影响。研究了三种前列腺癌（PCa）细胞系PC3-LN4，C4-2B和22Rv1。用CK2小分子抑制剂4,5,6处理PCa细胞，7-四溴苯并三唑和CX-4945，然后分析随时间变化的各个细胞区室中的Ca2 +水平。结果显示，胞浆中Ca2 +水平的剂量依赖性损失在2分钟内开始，并在5-10分钟内达到最大损失。内质网（ER）和线粒体区室中Ca2 +的增加。结果表明，CK2活性的抑制导致Ca2 +快速移出细胞质，进入ER和线粒体，这可能是导致受到CK2抑制的细胞凋亡诱导的最早因素之一。在具有诱导死亡的CK2抑制水平的细胞中，总细胞Ca2 +水平在治疗后2小时下降。这些新颖的观察结果代表了通过CK2活性调节细胞存活和死亡的潜在机制。