Document Detail

Triptolide sensitizes resistant cholangiocarcinoma cells to TRAIL-induced apoptosis.
MedLine Citation:
PMID:  16475706     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL/Apo2L) promotes apoptosis by binding to transmembrane receptors. It is known to induce apoptosis in a wide variety of cancer cells, but TRAIL-resistant cancers have also been documented. In this study, the relative resistance of human cholangiocarcinoma (CCA) cell lines against TRAIL-induced apoptosis is reported and the possible potential synergistic effect with triptolide, a diterpene triepoxide extracted from the Chinese herb Tripterygium wilfordii, in killing TRAIL-resistant CCA cells is investigated. MATERIALS AND METHODS: Six human CCA cell lines were treated with various concentrations of TRAIL and the resistant cells were identified and subsequently tested for their sensitivity to a combination of TRAIL and triptolide. The susceptibility and resistance of the cells were based on analysis of cytotoxic and apoptotic induction and expression of anti-apoptotic factors (Mcl-1 and cFLIP). RESULTS: The treatment of TRAIL induced a dose-dependent decrease in cell viability in 4 out of the 6 cell lines. A combination of TRAIL and triptolide enhanced cytotoxicity and apoptosis in these 2 resistant cell lines. The combined treatment enhanced activation of caspase-8 and its downstream signaling processes compared with the treatment with either one alone. CONCLUSION: The results presented show that human CCA cells were heterogeneous with respect to susceptibility to TRAIL-induced apoptosis. The combination of TRAIL and triptolide could enhance susceptibility to TRAIL-induced apoptotic killing in these TRAIL-resistant CCA cells, thus offering an alternative approach for the treatment of TRAIL-resistant cholangiocarcinoma.
Tasanee Panichakul; Pakamas Intachote; Adisak Wongkajorsilp; Banchob Sripa; Stitaya Sirisinha
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Anticancer research     Volume:  26     ISSN:  0250-7005     ISO Abbreviation:  Anticancer Res.     Publication Date:    2006 Jan-Feb
Date Detail:
Created Date:  2006-02-14     Completed Date:  2006-03-09     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  8102988     Medline TA:  Anticancer Res     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  259-65     Citation Subset:  IM    
Laboratory of Immunology, Chulabhom Research Institute, Bangkok, Thailand.
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MeSH Terms
Antineoplastic Combined Chemotherapy Protocols / pharmacology*
Apoptosis / drug effects*
Apoptosis Regulatory Proteins / administration & dosage,  pharmacology*
Caspase 8
Caspases / metabolism
Cell Line, Tumor
Cholangiocarcinoma / drug therapy*,  pathology
Diterpenes / administration & dosage,  pharmacology*
Down-Regulation / drug effects
Drug Resistance, Neoplasm
Drug Synergism
Enzyme Activation / drug effects
Epoxy Compounds
Membrane Glycoproteins / administration & dosage,  pharmacology*
Mitogen-Activated Protein Kinase 1 / metabolism
Neoplasm Proteins / metabolism
Phenanthrenes / administration & dosage,  pharmacology*
Proto-Oncogene Proteins c-bcl-2 / metabolism
TNF-Related Apoptosis-Inducing Ligand
Tumor Necrosis Factor-alpha / administration & dosage,  pharmacology*
Reg. No./Substance:
0/Apoptosis Regulatory Proteins; 0/Diterpenes; 0/Epoxy Compounds; 0/Membrane Glycoproteins; 0/Neoplasm Proteins; 0/Phenanthrenes; 0/Proto-Oncogene Proteins c-bcl-2; 0/TNF-Related Apoptosis-Inducing Ligand; 0/TNFSF10 protein, human; 0/Tumor Necrosis Factor-alpha; 0/myeloid cell leukemia sequence 1 protein; 38748-32-2/triptolide; EC Protein Kinase 1; EC 3.4.22.-/CASP8 protein, human; EC 3.4.22.-/Caspase 8; EC 3.4.22.-/Caspases

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