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 in hibitor, could specifically inhibit the activity of proteinase In and lead to growth arrest of Hela cells in early S phase. In this study, A PCA-OPhBut exhibited inhibitory effects on the growth of HL-60 cells. Apoptotic cells were observed when the cells were cultured with APCA-O PhBut above 50 mu M. Time course studies demonstrated that apoptotic c ells were increased in a dose- and time-dependent manner. Flowcytometr ic assays demonstrated that HL-60 cells underwent slight G1 growth arr est after treatment with APCA-OPhBut. No change of Bcl-2 protein level was detected. The findings suggest that the intracellular trypsin-lik e protease inhibited by APCA-OPhBut not only plays a key role in DNA s ynthesis initiation but is also necessary for survival of certain cell lines.