TY - JOUR T1 - Caspase-3 Activation and Induction of PARP Cleavage by Cyclic Dipeptide Cyclo(Phe-Pro) in HT-29 Cells JF - Anticancer Research JO - Anticancer Res SP - 4197 LP - 4202 VL - 25 IS - 6B AU - SETH CLINT BRAUNS AU - GILL DEALTRY AU - PIETER MILNE AU - RYNO NAUDÉ AU - MARYNA VAN DE VENTER Y1 - 2005/11/01 UR - http://ar.iiarjournals.org/content/25/6B/4197.abstract N2 - Background: Cyclo(Phe-Pro) has been shown to inhibit cancer cell growth and induce apoptosis in HT-29 colon cancer cells. Materials and Methods: The molecular mechanisms mediating cyclo(Phe-Pro)-induced apoptosis in HT-29 cells were investigated. Cells were treated with 5 mM or 10 mM cyclo(Phe-Pro) for varying times. Immunoblot analysis was used to detect poly(ADP-ribose)polymerase (PARP) cleavage. A fluorescence-based enzymatic assay was used to measure caspase-3 activity. Results: Cyclo(Phe-Pro) (10 mM) induced time-dependent cleavage of PARP, detected as early as 8 hours post treatment. PARP cleavage was blocked by co-administration with the broad-range caspase inhibitor Z-VAD-FMK. Cyclo(Phe-Pro) also induced a time-dependent increase (p<0.01) in caspase-3 activity. This increase in activity was blocked in the presence of the caspase-3 inhibitor Ac-DEVD-CHO. Conclusion: These results provide evidence that cyclo(Phe-Pro)-induced apoptosis in HT-29 cells is mediated by a caspase cascade. These findings warrant further investigation into the potential antitumour activity of cyclo(Phe-Pro) and its related cyclic dipeptide derivatives. Copyright© 2005 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved ER -