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

Abstract

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. 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 (Δψm). Cells treated with the CK2 inhibitors TBB (4,5,6,7-tetrabromobenzotriazole) or TBCA (tetrabromocinnamic acid) demonstrate changes in Δψm 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 Δψm. Further, we have demonstrated the presence of CK2 in purified mitochondria and it appears that the effect on Δψm 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 Δψm and mitochondrial permeability. Thus, we propose that a key mechanism of CK2 impact on mitochondrial apoptotic circuitry and cell death involves early loss of Δψm which may be a primary trigger for apoptotic signaling and cell death resulting from CK2 inhibition.

Growth inhibition and apoptosis in cancer cells induced by polyphenolic compounds of Acacia hydaspica: Involvement of multiple signal transduction pathways

“…CellTiter 96 ® Aqueous One assay was used to assess cell viability as previously described 43 . MDA-MB 231 and PC-3 cells were seeded into 96-well plates at 1.5 and 2.5 × 10 4 cells/well, respectively.…”

“…PC-3 and MDA-MB-231 cells were collected after AHC treatments for 48 h, suspended in fresh medium, quantified, and 500 cells (MDA-MB-231) or 1000 cells (PC-3) were plated in triplicate into 35 mm cell culture dishes. After 7 days, colonies were stained with crystal violet as previously described 43 . Colonies were counted under dark field using a cubic colony counter (AO scientific).…”

Protective effects of Monotheca buxifolia fruit on renal toxicity induced by CCl4 in rats

“…Survival assay against the MBM was carried out on the nauplii of brine shrimp ( Artemia salina ). For this purpose brine shrimp eggs were hatched in artificial sea water by dissolving 38 g/l of sea salt in distilled water [ 16 ]. A lamp was placed above the open side of the tank to attract the hatched shrimps towards wall of the tank.…”

Ikaros mediates the DNA methylation-independent silencing of MCJ/DNAJC15 gene expression in macrophages

“…It has also been reported that IFNγ regulates the expression of a subset of genes through the activation of CK2 21 22 . To investigate whether IFNγ promotes Ikaros binding through CK2, cells were treated with IFNγ in the presence of a CK2 specific inhibitor, 4,5,6,7-tetrabromobenzotriazole (TBB) 23 . CHIP analysis demonstrated that the pretreatment with TBB abrogated IFNγ-induced binding of Ikaros to the MCJ promoter ( Fig.…”