| Dykellic acid inhibits drug-induced caspase-3-like protease activation. | |
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MedLine Citation:
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PMID: 12615068 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Dykellic acid is a novel microbial metabolite isolated from the broth of Westerdykella multispora F50733. Investigations on the molecular function of dykellic acid revealed that this compound partially inhibits calcium influx, resulting in a decrease in Ca(2+)-dependent endonuclease activation and DNA fragmentation induced by camptothecin. In our experiments, active caspase-3-like protease cleavage of procaspase-3, PARP, and cytosolic cytochrome c was inhibited by dykellic acid in a concentration-dependent manner when the apoptosis was induced by camptothecin as well as doxorubicin. We confirmed that dykellic acid did not bind to camptothecin using surface plasmon resonance analysis. These results suggest that dykellic acid inhibits drug-induced apoptosis via a caspase-3-like protease-suppressing mechanism. Our data provide important information on the mechanism of action of dykellic acid and indicate that this compound may be employed in the treatment of specific caspase-3-like protease-mediated diseases. |
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Authors:
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Sang-Han Lee; Eun-Soo Youk; Ho-Jae Lee; Yung-Hee Kho; Hwan Mook Kim; Sung-Uk Kim |
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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: Biochemical and biophysical research communications Volume: 302 ISSN: 0006-291X ISO Abbreviation: Biochem. Biophys. Res. Commun. Publication Date: 2003 Mar |
Date Detail:
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Created Date: 2003-03-04 Completed Date: 2003-05-13 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0372516 Medline TA: Biochem Biophys Res Commun Country: United States |
Other Details:
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Languages: eng Pagination: 539-44 Citation Subset: IM |
Affiliation:
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Korea Research Institute of Bioscience & Biotechnology, Taejon 305-333, Republic of Korea. sang@mail.kribb.re.kr |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Apoptosis Blotting, Western Calcium / metabolism Camptothecin / metabolism, pharmacology Caspase 3 Caspases / metabolism* Cell Line Cytochrome c Group / metabolism Cytosol / enzymology DNA Fragmentation Dose-Response Relationship, Drug Endonucleases / metabolism Enzyme Activation Enzyme Precursors / metabolism HL-60 Cells Humans Jurkat Cells Microscopy, Electron, Scanning Models, Chemical Poly(ADP-ribose) Polymerases / metabolism Propionates / pharmacology* Pyrones / pharmacology* Spectrometry, Fluorescence Surface Plasmon Resonance Time Factors U937 Cells |
| Chemical | |
Reg. No./Substance:
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0/Cytochrome c Group; 0/Enzyme Precursors; 0/Propionates; 0/Pyrones; 0/dykellic acid; 7440-70-2/Calcium; 7689-03-4/Camptothecin; EC 2.4.2.30/Poly(ADP-ribose) Polymerases; EC 3.1.-/Endonucleases; 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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