Thus, we propose that a key mechanism of CK2 impact on mitochondrial apoptotic circuitry and cell death involves early loss of Δψ m which may be a primary trigger for apoptotic signaling and cell death resulting from CK2 inhibition. Results also suggest that alterations in Ca 2+ signaling may be involved in the CK2 mediated regulation of Δψ m and mitochondrial permeability. Further, we have demonstrated the presence of CK2 in purified mitochondria and it appears that the effect on Δψ m evoked by inhibition of CK2 may involve mitochondrial localized CK2. Cells treated with the CK2 inhibitors TBB (4,5,6,7-tetrabromobenzotriazole) or TBCA (tetrabromocinnamic acid) demonstrate changes in Δψ m which become apparent within 2 h, i.e., significantly prior to evidence of activation of other mitochondrial apoptotic signals whose temporal expression ensues subsequent to loss of Δψ m. 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 (Δψ m). CK2 downregulation is known to impact mitochondrial apoptotic circuitry but the underlying mechanism(s) remain unclear. CK2 (official acronym for casein kinase 2 or II) is a potent suppressor of apoptosis in response to diverse apoptotic stimuli -thus its molecular downregulation or activity inhibition results in potent induction of cell death.
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