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.