Sensitization of cancer cells to DNA damage-induced cell death by specificcell cycle G(2) checkpoint abrogation

We devised two short peptides corresponding to amino acids 211-221 of human Cdc25C fused with a part of HIV1-TAT. These peptides inhibited hChk1 and C hk2/HuCds1 kinase activity in vitro and specifically abrogated the G(2) che ckpoint in vivo. These peptides sensitized p53-defective cancer cell lines to DNA-damaging agent to death without obvious cytotoxic effect on normal c ells. Our results clearly indicate that the specific abrogation of the cell cycle G(2) checkpoint is a feasible strategy for cancer therapy, and hChk1 and Chk2/HuCds1 are proper targets for that purpose.