Protein Kinase CK2 Inhibition Induces Cell Death via Early Impact on Mitochondrial Function

CK2 (official acronym for casein kinase 2 or II) is a potent suppressor of apoptosis in response to diverse apoptotic stimulithus its molecular downregulation or activity inhibition results in potent induction of cell death. CK2 downregulation is known to impact mitochondrial apoptotic circuitry but the underlying mechanism(s) remain unclear. Utilizing prostate cancer cell lines subjected to CK2-specific inhibitors which cause loss of cell viability, we have found that CK2 inhibition in cells causes rapid early decrease in mitochondrial membrane potential ((m)). Cells treated with the CK2 inhibitors TBB (4,5,6,7-tetrabromobenzotriazole) or TBCA (tetrabromocinnamic acid) demonstrate changes in (m) which become apparent within 2h, that is, significantly prior to evidence of activation of other mitochondrial apoptotic signals whose temporal expression ensues subsequent to loss of (m). Further, we have demonstrated the presence of CK2 in purified mitochondria and it appears that the effect on (m) evoked by inhibition of CK2 may involve mitochondrial localized CK2. Results also suggest that alterations in Ca2+ signaling may be involved in the CK2 mediated regulation of (m) and mitochondrial permeability. Thus, we propose that a key mechanism of CK2 impact on mitochondrial apoptotic circuitry and cell death involves early loss of (m) which may be a primary trigger for apoptotic signaling and cell death resulting from CK2 inhibition. J. Cell. Biochem. 115: 2103-2115, 2014. (c) 2014 Wiley Periodicals, Inc.