Fig. 7. A cartoon depicting the proposed sequence of events in cells treated with CK2 inhibitors that lead to induction of apoptosis.

It is proposed that among the earliest changes in response to treatment of cells with CK2 inhibitors is the effect on mitochondrial membrane permeability transition associated with Ca²⁺ flux (before 2 h) and loss of mitochondrial membrane potential which occur as early as 2 h following the treatment of cells with TBB (earliest practical time measurements in this experimental model). The subsequent series of events that become apparent between 6 to 24 h following inhibition of CK2 appear to be production of ROS, loss of cell viability, and loss of proliferative capacity (by 4–6 h) followed by other apoptotic signals such as activation of caspases, cleavage of lamin A/C, loss of phospho-Ser129 and total AKT-1, release of cytochrome c and Cox IV from mitochondria, and loss of IAPs expression observed by 24 h [Tapia et al., 2006; Wang et al., 2008].