Influence of p53 and p21(WAF1) expression on sensitivity of cancer cells to cladribine.

The present study was performed to gain insight into the role of p53 and p21(WAF1) on the cytotoxicity of the purine analogue cladribine (2-CdA) on cancer cells. Drug sensitivity, cell cycle distribution and drug-induced cell death were compared in three lines derived from the colorectal carcinoma HCT116: the p53+/+ cell line containing wild-type p53 and the p53-/- and p21(WAF1)-/- lines, in which both alleles of p53 or p21(WAF1) were deleted by homologous recombination, respectively. p53-/- and p21(WAF1)-/- cells were significantly more resistant to the cytotoxic effects of 2-CdA than the p53+/+ cells.