| Resveratrol-induced apoptotic death in human U251 glioma cells. | |
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MedLine Citation:
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PMID: 15827328 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Resveratrol (trans-3,4',5-trihydroxystilbene) is a naturally occurring polyphenolic compound highly enriched in grapes, peanuts, red wine, and a variety of food sources. Resveratrol has antiinflammatory and antioxidant properties, and also has potent anticancer properties. Human glioma U251 cells were used to understand the molecular mechanisms by which resveratrol acts as an anticancer agent, since glioma is a particularly difficult cancer to treat and eradicate. Our data show that resveratrol induces dose- and time-dependent death of U251 cells, as measured by lactate dehydrogenase release and internucleosomal DNA fragmentation assays. Resveratrol induces activation of caspase-3 and increases the cleavage of the downstream caspase substrate, poly(ADP-ribose) polymerase. Resveratrol-induced DNA fragmentation can be completely blocked by either a general caspase inhibitor (Z-VAD-FMK) or a selective caspase-3 inhibitor (Z-DEVD-FMK), but not by a selective caspase-1 inhibitor. Resveratrol induces cytochrome c release from mitochondria to the cytoplasm and activation of caspase-9. Resveratrol also increases expression of proapoptotic Bax and its translocation to the mitochondria. Resveratrol inhibits U251 proliferation, as measured by MTS assay [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt], and induces G0/G1 growth arrest, as determined by flow cytometry. The cyclin-dependent kinase inhibitor, olomoucine, prevents cell cycle progression and resveratrol-induced apoptosis. These results suggest that multiple signaling pathways may underlie the apoptotic death of U251 glioma induced by resveratrol, which warrants further exploration as an anticancer agent in human glioma. |
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Authors:
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Hao Jiang; Lijie Zhang; Jarret Kuo; Kelly Kuo; Subhash C Gautam; Laurent Groc; Alba I Rodriguez; David Koubi; Tangella Jackson Hunter; George B Corcoran; Michael D Seidman; Robert A Levine |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Molecular cancer therapeutics Volume: 4 ISSN: 1535-7163 ISO Abbreviation: Mol. Cancer Ther. Publication Date: 2005 Apr |
Date Detail:
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Created Date: 2005-04-13 Completed Date: 2005-10-06 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 101132535 Medline TA: Mol Cancer Ther Country: United States |
Other Details:
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Languages: eng Pagination: 554-61 Citation Subset: IM |
Affiliation:
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William T. Gossett Neurology Laboratories, Henry Ford Health System, Detroit, Michigan 48202, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Amino Acid Chloromethyl Ketones
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pharmacology Antineoplastic Agents, Phytogenic / pharmacology Apoptosis* Blotting, Western Caspase 3 Caspase 9 Caspases / antagonists & inhibitors, metabolism Cell Cycle Cell Line, Tumor Cytochromes c / metabolism Cytoplasm / metabolism DNA Fragmentation Dose-Response Relationship, Drug Enzyme Activation Enzyme Inhibitors / pharmacology Flavonoids Glioma / drug therapy*, pathology* Humans Kinetin L-Lactate Dehydrogenase / metabolism Phenols Poly(ADP-ribose) Polymerases / metabolism Proto-Oncogene Proteins c-bcl-2 / metabolism Purines / pharmacology Signal Transduction Stilbenes / pharmacology* Subcellular Fractions Time Factors Up-Regulation bcl-2-Associated X Protein |
| Chemical | |
Reg. No./Substance:
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0/Amino Acid Chloromethyl Ketones; 0/Antineoplastic Agents, Phytogenic; 0/BAX protein, human; 0/Enzyme Inhibitors; 0/Flavonoids; 0/Phenols; 0/Proto-Oncogene Proteins c-bcl-2; 0/Purines; 0/Stilbenes; 0/bcl-2-Associated X Protein; 0/benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; 0/olomoucine; 0/polyphenols; 501-36-0/resveratrol; 525-79-1/Kinetin; 9007-43-6/Cytochromes c; EC 1.1.1.27/L-Lactate Dehydrogenase; EC 2.4.2.30/Poly(ADP-ribose) Polymerases; EC 3.4.22.-/CASP3 protein, human; EC 3.4.22.-/CASP9 protein, human; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspase 9; EC 3.4.22.-/Caspases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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