Sensitization of cancer cells to DNA damage-induced cell death by specific cell cycle G2 checkpoint abrogation.
作者:Masashi Suganuma, Takumi Kawabe, Haruna Hori, Takahiko Funabiki, Takashi Okamoto · 发表于:PubMed · 年份:1999 · 被引用次数:103 · 研究领域:Cancer-related Molecular Pathways、Ubiquitin and proteasome pathways、RNA modifications and cancer
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.