| Caspase-3 activation and induction of PARP cleavage by cyclic dipeptide cyclo(Phe-Pro) in HT-29 cells. | |
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MedLine Citation:
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PMID: 16309216 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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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Authors:
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Seth Clint Brauns; Gill Dealtry; Pieter Milne; Ryno Naudé; Maryna Van de Venter |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Anticancer research Volume: 25 ISSN: 0250-7005 ISO Abbreviation: Anticancer Res. Publication Date: 2005 Nov-Dec |
Date Detail:
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Created Date: 2005-11-28 Completed Date: 2006-01-05 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 8102988 Medline TA: Anticancer Res Country: Greece |
Other Details:
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Languages: eng Pagination: 4197-202 Citation Subset: IM |
Affiliation:
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Department of Biochemistry and Microbiology, Nelson Mandela Metropolitan University, Port Elizabeth, 6031, South Africa. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Amino Acid Chloromethyl Ketones
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pharmacology Caco-2 Cells Caspase 3 Caspases / antagonists & inhibitors, biosynthesis, metabolism* Cysteine Proteinase Inhibitors / pharmacology Dipeptides / pharmacology*, toxicity Enzyme Activation / drug effects Enzyme Induction / drug effects HT29 Cells Humans Peptides, Cyclic / pharmacology*, toxicity Poly(ADP-ribose) Polymerases / metabolism* |
| Chemical | |
Reg. No./Substance:
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0/Amino Acid Chloromethyl Ketones; 0/Cysteine Proteinase Inhibitors; 0/Dipeptides; 0/Peptides, Cyclic; 0/benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; 0/cyclo(phenylalanyl-prolyl); EC 2.4.2.30/Poly(ADP-ribose) Polymerases; EC 3.4.22.-/CASP3 protein, human; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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