Effects of amidinopiperidine-4-carboxylic acid 4-tert-butylphenyl ester, a specific trypsin inhibitor, on the growth of HL-60 cells.
Previous results showed that the synthetic compound amidinopiperidine-4-carboxylic acid 4-tert-butylphenyl ester (APCA-OPhBut), a trypsin inhibitor, could specifically inhibit the activity of proteinase In and lead to growth arrest of Hela cells in early S phase. In this study, APCA-OPhBut exhibited inhibitory effects on the growth of HL-60 cells. Apoptotic cells were observed when the cells were cultured with APCA-OPhBut above 50 microM. Time course studies demonstrated that apoptotic cells were increased in a dose- and time-dependent manner. Flowcytometric assays demonstrated that HL-60 cells underwent slight G1 growth arrest after treatment with APCA-OPhBut. No change of Bcl-2 protein level was detected. The findings suggest that the intracellular trypsin-like protease inhibited by APCA-OPhBut not only plays a key role in DNA synthesis initiation but is also necessary for survival of certain cell lines.
Department of Biochemistry, Nanjing University, P. R. China.
M
M
Zhang
J
J
Zhu
D
D
Zhu
M
M
Muramatu
D017209:Apoptosis / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D016193:G1 Phase / Q000187:drug effects; D018922:HL-60 Cells; D006801:Humans; D007540:Isonipecotic Acids / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D014361:Trypsin Inhibitors / Q000494:pharmacology*
D007540:Isonipecotic Acids; D019253:Proto-Oncogene Proteins c-bcl-2; D014361:Trypsin Inhibitors; C082994:amidinopiperidine-4-carboxylic acid 4-tert-butylphenyl ester