In cells with death-inducing levels of CK2 inhibition, total cellular Ca 2+ levels dropped at 2 h post-treatment. The results suggest that inhibition of CK2 activity results in a rapid movement of Ca 2+ 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. There was a concomitant increase in Ca 2+ in the endoplasmic reticulum (ER) and mitochondrial compartments. The results showed dose-dependent loss in cytosolic Ca 2+ levels starting within 2 min and reaching maximal loss within 5–10 min. PCa cells were treated with the CK2 small molecule inhibitors 4,5,6,7-tetrabrombenzotriazole and CX-4945 followed by analysis of Ca 2+ levels in various cellular compartments over time. Three prostate cancer (PCa) cell lines, PC3-LN4, C4-2B, and 22Rv1, were studied. Thus, in the present work, we investigated early impact of CK2 on intracellular Ca 2+ dynamics. One of the earliest responses of prostate cells to inhibition of CK2 is a change in mitochondrial membrane potential, possibly associated with Ca 2+ signaling. 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.
CK2 is elevated in numerous types of cancer cells, and CK2 suppression of apoptosis represents a key link to the cancer cell phenotype.
Protein kinase CK2 plays multiple roles in cell function in normal and disease states.
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