Document Detail


Triptolide circumvents drug-resistant effect and enhances 5-fluorouracil antitumor effect on KB cells.
MedLine Citation:
PMID:  20154595     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Triptolide, a diterpenoid triepoxide derived from the Chinese herb Tripterygium wilfordii, exerts an antitumor effect in KB cancer cells through the induction of apoptosis. In this study, we show that triptolide possesses an anticancer effect on drug-sensitive parental KB cells and multidrug-resistant KB-7D and KB-tax cells that overexpress multidrug resistance protein and MDR, respectively. Our data revealed that triptolide decreases the expression of multidrug resistance protein and MDR in both KB-7D and KB-tax cells. It also induces apoptosis in these multidrug-resistant cancer cells by activating caspase-3, and decreasing Mcl-1 and XIAP. Triptolide not only inhibits tumor growth but also induces apoptosis of these drug-resistant cancer cells in xenograft mouse models. Moreover, we also show that triptolide combined with 5-fluorouracil could be an alternative strategy for chemotherapy enhancement. These results indicate the therapeutic value of triptolide on multidrug-resistant cells, and when combined with 5-fluorouracil for the enhancement of cancer therapy.
Authors:
Yuan-Wu Chen; Gu-Jiun Lin; Yi-Ping Chuang; Wei-Tso Chia; Dueng-Yuan Hueng; Chih-Kung Lin; Shin Nieh; Huey-Kang Sytwu
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Anti-cancer drugs     Volume:  21     ISSN:  1473-5741     ISO Abbreviation:  Anticancer Drugs     Publication Date:  2010 Jun 
Date Detail:
Created Date:  2010-04-14     Completed Date:  2010-05-13     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9100823     Medline TA:  Anticancer Drugs     Country:  England    
Other Details:
Languages:  eng     Pagination:  502-13     Citation Subset:  IM    
Affiliation:
Graduate Institute of Medical Sciences, National Defense Medical Center, Taiwan, Republic of China.
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MeSH Terms
Descriptor/Qualifier:
Antineoplastic Combined Chemotherapy Protocols / pharmacology*
Apoptosis / drug effects
Body Weight / drug effects
Caspase 3 / metabolism
Diterpenes / pharmacology*
Down-Regulation / drug effects
Drug Resistance, Neoplasm / drug effects
Drug Screening Assays, Antitumor
Drug Synergism
Epoxy Compounds / pharmacology
Fluorouracil / pharmacology*
Humans
KB Cells
P-Glycoprotein / metabolism
Phenanthrenes / pharmacology*
Proto-Oncogene Proteins c-bcl-2 / antagonists & inhibitors,  metabolism
X-Linked Inhibitor of Apoptosis Protein / antagonists & inhibitors,  metabolism
Chemical
Reg. No./Substance:
0/Diterpenes; 0/Epoxy Compounds; 0/P-Glycoprotein; 0/Phenanthrenes; 0/Proto-Oncogene Proteins c-bcl-2; 0/X-Linked Inhibitor of Apoptosis Protein; 0/myeloid cell leukemia sequence 1 protein; 38748-32-2/triptolide; 51-21-8/Fluorouracil; EC 3.4.22.-/Caspase 3

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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