We have shown previously that down-regulation of CK2 activity (
protein kinase CK2, formerly
casein kinase 2) by employing its inhibitors
apigenin or
4,5,6,7-tetrabromobenzotriazole promotes apoptosis in prostatic
carcinoma cells. In an effort to define the downstream mediators of this action, we show that cell apoptosis observed on down-regulation of CK2 is preceded by intracellular generation of
hydrogen hydroxide (H2O2) in various normal and
cancer cells. In this regard, both
androgen-dependent ALVA-41 and
androgen-independent PC-3 cells treated with 80 micromol/L
apigenin or
4,5,6,7-tetrabromobenzotriazole or with antisense CK2alpha
oligonucleotide or
small interfering RNA respond similarly to down-regulation of CK2. Interestingly, whereas chemical inhibitors of CK2 elicited H2O2 production in both
cancer and noncancer cells, the antisense CK2alpha-mediated down-regulation of CK2 showed significant H2O2 production in
cancer cells but had minimal effect in noncancer cells. The basis of this key difference is unclear at present, but this observation may have implications for the therapeutic potential of antisense CK2
oligonucleotide in
cancer therapy. The H2O2 production induced by antisense CK2alpha was associated with robust
caspase-3 activity,
nuclear factor-kappaB nuclear translocation,
cytochrome c release, and subsequent DNA fragmentation in
prostate cancer cells (ALVA-41 and PC-3). These findings describe, for the first time, a relationship between CK2 and
reactive oxygen species, such that CK2 inhibition leads to production of intracellular H2O2, which may serve as a downstream mediator of apoptosis in
cancer cells.