| Mechanism of triptolide-induced apoptosis: Effect on caspase activation and Bid cleavage and essentiality of the hydroxyl group of triptolide. | |
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MedLine Citation:
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PMID: 16385419 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Triptolide is a compound extracted from the Chinese herb Tripterygium wilfordii Hook. f. Triptolide has potent anticancer activity. However, the mechanisms by which triptolide exerts its anticancer activities remain unclear. To explore the molecular mechanisms involved in the anticancer activity of triptolide, we have examined the effect of triptolide on the growth of pancreatic carcinoma PANC-1 and cervical adenocarcinoma HeLa cells. We found that treatment of both HeLa and PANC-1 cells with triptolide potently suppressed cell growth and induced apoptosis, indicated by nuclear fragmentation and blebbing. In both HeLa and PANC-1 cells, apoptosis induced by triptolide was associated with activation of both caspase-3 and caspase-8, and cleavage of poly(ADP-ribose) polymerase and Bid. Moreover, in HeLa cells, caspase-9 is also significantly activated in response to triptolide. Overexpression of Bcl-2 in HeLa cells substantially attenuated triptolide-induced apoptosis. Interestingly, substitution of the 14-OH of triptolide with an acetyl group abrogated both its anticancer and its antiinflammatory activities. Our studies suggest that triptolide may exert its anticancer effects by initiating apoptosis through both death-receptor- and mitochondria-mediated pathways. Our results indicate that both the apoptosis-promoting and the antiinflammatory activities of triptolide depend on the 14-OH group. |
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Authors:
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Xianxi Wang; Ranyia Matta; Gang Shen; Leif D Nelin; Dehua Pei; Yusen Liu |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2005-12-30 |
Journal Detail:
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Title: Journal of molecular medicine (Berlin, Germany) Volume: 84 ISSN: 0946-2716 ISO Abbreviation: J. Mol. Med. Publication Date: 2006 May |
Date Detail:
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Created Date: 2006-05-01 Completed Date: 2007-01-30 Revised Date: 2011-07-08 |
Medline Journal Info:
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Nlm Unique ID: 9504370 Medline TA: J Mol Med (Berl) Country: Germany |
Other Details:
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Languages: eng Pagination: 405-15 Citation Subset: IM |
Affiliation:
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Department of Pediatrics, Center for Developmental Pharmacology and Toxicology, Children's Research Institute, The Ohio State University, Columbus, OH 43205, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Anti-Inflammatory Agents, Non-Steroidal
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chemistry,
pharmacology Antineoplastic Agents, Alkylating / chemistry, pharmacology* Apoptosis / drug effects* BH3 Interacting Domain Death Agonist Protein / drug effects, metabolism* Carcinoma / drug therapy, pathology Caspases / drug effects*, metabolism Diterpenes / chemistry*, pharmacology* Enzyme Activation / drug effects Epoxy Compounds Hela Cells Humans Pancreatic Neoplasms / drug therapy, pathology Phenanthrenes / chemistry*, pharmacology* Proto-Oncogene Proteins c-bcl-2 / drug effects, genetics, metabolism Structure-Activity Relationship Tumor Cells, Cultured |
| Grant Support | |
ID/Acronym/Agency:
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R01AI57798/AI/NIAID NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Anti-Inflammatory Agents, Non-Steroidal; 0/Antineoplastic Agents, Alkylating; 0/BH3 Interacting Domain Death Agonist Protein; 0/BID protein, human; 0/Diterpenes; 0/Epoxy Compounds; 0/Phenanthrenes; 0/Proto-Oncogene Proteins c-bcl-2; 38748-32-2/triptolide; EC 3.4.22.-/Caspases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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