Sensitization of cancer cells to DNA damage-induced cell death by specific cell cycle G2 checkpoint abrogation.

Suganuma, M; Kawabe, T; Hori, H; Funabiki, T; Okamoto, T · Cancer Res · 1999

basic_science · Level V

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Abstract

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 Chk2/HuCds1 kinase activity in vitro and specifically abrogated the G2 checkpoint in vivo. These peptides sensitized p53-defective cancer cell lines to DNA-damaging agent to death without obvious cytotoxic effect on normal cells. Our results clearly indicate that the specific abrogation of the cell cycle G2 checkpoint is a feasible strategy for cancer therapy, and hChk1 and Chk2/HuCds1 are proper targets for that purpose.

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