| Essential role of caspases in epigallocatechin-3-gallate-mediated inhibition of nuclear factor kappa B and induction of apoptosis. | |
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MedLine Citation:
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PMID: 14676829 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Green tea constituent (-) epigallocatechin-3-gallate (EGCG) has shown remarkable cancer-preventive and some cancer-therapeutic effects. This is partially because of its ability to induce apoptosis in cancer cells without affecting normal cells. Previous studies from our laboratory have shown the involvement of NF-kappa B pathway in EGCG-mediated cell-cycle deregulation and apoptosis of human epidermoid carcinoma A431 cells. Here we show the essential role of caspases in EGCG-mediated inhibition of NF-kappa B and its subsequent apoptosis. Treatment of A431 cells with EGCG (10-40 microg/ml) resulted in dose-dependent inhibition of NF-kappa B/p65, induction of DNA breaks, cleavage of poly(ADP-ribose) polymerase (PARP) and morphological changes consistent with apoptosis. EGCG treatment of cells also resulted in significant activation of caspases, as shown by the dose- and time-dependent increase in DEVDase activity, and protein expression of caspase-3, -8 and -9. EGCG-mediated caspase activation induces proteolytic cleavage of NF-kappa B/p65 subunit, leading to the loss of transactivation domains, and driving the cells towards apoptosis. EGCG-mediated induction of apoptosis was significantly blocked by the caspase inhibitor N-benzyloxycarbonyl-Val-Ala-Asp(OMe)-fluoromethylketone (Z-VAD-FMK), and moderately blocked by the specific caspase-3 inhibitor Z-DEVD-FMK. Further, pretreatment of cells with Z-VAD-FMK was found to suppress the cleavage of NF-kappa B/p65 subunit, thereby increasing nuclear translocation, DNA binding and transcriptional activity, thus protecting the cells from EGCG-induced apoptosis. Taken together, these studies for the first time demonstrate that EGCG-mediated activation of caspases is critical, at least in part, for inhibition of NF-kappa B and subsequent apoptosis. |
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Authors:
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Sanjay Gupta; Kedar Hastak; Farrukh Afaq; Nihal Ahmad; Hasan Mukhtar |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Oncogene Volume: 23 ISSN: 0950-9232 ISO Abbreviation: Oncogene Publication Date: 2004 Apr |
Date Detail:
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Created Date: 2004-04-01 Completed Date: 2004-04-27 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 8711562 Medline TA: Oncogene Country: England |
Other Details:
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Languages: eng Pagination: 2507-22 Citation Subset: IM |
Affiliation:
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Department of Urology, Case Western Reserve University, Cleveland, OH 44106, 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 Apoptosis / drug effects* Carcinoma, Squamous Cell Caspases / antagonists & inhibitors, metabolism* Catechin / analogs & derivatives*, pharmacology* Cell Line, Tumor Cell Nucleus / metabolism Cell Survival DNA / metabolism Dose-Response Relationship, Drug Enzyme Activation Humans Male Models, Biological NF-kappa B / antagonists & inhibitors*, chemistry, metabolism Oligopeptides / pharmacology Poly(ADP-ribose) Polymerases / drug effects Prostatic Neoplasms Protein Structure, Tertiary / drug effects Time Factors Transcription, Genetic |
| Grant Support | |
ID/Acronym/Agency:
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R01 CA 78809/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Amino Acid Chloromethyl Ketones; 0/NF-kappa B; 0/Oligopeptides; 0/benzoylcarbonyl-aspartyl-glutamyl-valyl-aspartyl-fluoromethyl ketone; 0/benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; 154-23-4/Catechin; 9007-49-2/DNA; 989-51-5/epigallocatechin gallate; EC 2.4.2.30/Poly(ADP-ribose) Polymerases; EC 3.4.22.-/Caspases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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