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  • Title: Caspase-3 activation and induction of PARP cleavage by cyclic dipeptide cyclo(Phe-Pro) in HT-29 cells.
    Author: Brauns SC, Dealtry G, Milne P, Naudé R, Van de Venter M.
    Journal: Anticancer Res; 2005; 25(6B):4197-202. PubMed ID: 16309216.
    Abstract:
    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.
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