We have previously shown that the down-regulation of protein kinase CKII activity is tightly associated with cellular senescence of human fibroblast IMR-90 cells. Here, we examined the roles of p53 and p21^Cip1/WAF1 in senescence development induced by CKII inhibition using wild-type, isogenic p53-/- and isogenic p21-/- HCT116 human colon cancer cell lines. A senescent marker appeared after staining for senescence-associated β-galactosidase activity in wild-type HCT116 cells treated with CKII inhibitor or CKIIα siRNA, but this response was almost abolished in p53- or p21Cip1/WAF1-null cells. Increased cellular levels of p53 and p21^Cip1/WAF1 protein occurred with the inhibition of CKII. CKII inhibition upregulated p53 and p21^Cip1/WAF1 expression at post-transcriptional level and transcription level, respec-tively. RB phosphorylation significantly decreased in cells treated with CKII inhibitor. Taken together, this study shows that the activation of the p53-p21^Cip1/WAF1 pathway acts as a major mediator of cellular senescence induced by CKII inhibition.

Keywords: human colon cancer cell, p21Cip1/WAF1, p53, protein kinase CKII, senescence