Document Detail


Tannic acid synergizes the cytotoxicity of chemotherapeutic drugs in human cholangiocarcinoma by modulating drug efflux pathways.
MedLine Citation:
PMID:  17069924     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND/AIMS: Tannic acid is an orally active plant polyphenol with potential for use as an anti-cancer agent for cholangiocarcinoma. To determine the potential use of tannic acid as an adjunct therapy, we sought to evaluate the interaction between tannic acid and chemotherapeutic agents.
METHODS: Cytotoxicity was assessed in malignant human cholangiocytes. Interactions between tannic acid, mitomycin C, 5-fluorouracil and gemcitabine were quantitated by calculating the combination index and dose reduction index. Cellular efflux pathways were assessed by calcein retention assays, and expression of membrane pumps was assessed by Western blots and real-time PCR.
RESULTS: Tannic acid and the three agents decreased growth of malignant cholangiocytes to a similar extent. Tannic acid had a synergistic effect to mitomycin C and 5-fluorouracil, but not gemcitabine. However, the structurally related polyphenol gallic acid did not have a synergistic interaction with any of the agents. Tannic acid decreased calcein efflux and the expression of PGP, MRP1 and MRP2 membrane efflux pumps.
CONCLUSIONS: Tannic acid has a synergistic effect with selected chemotherapeutic drugs by a mechanism involving modulation of drug efflux pathways. Thus, tannic acid will be a useful adjunct to improve the effectiveness of chemotherapeutic agents in the treatment of cholangiocarcinoma.
Authors:
Peter J Naus; Roger Henson; Grant Bleeker; Hania Wehbe; Fanyin Meng; Tushar Patel
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2006-10-06
Journal Detail:
Title:  Journal of hepatology     Volume:  46     ISSN:  0168-8278     ISO Abbreviation:  J. Hepatol.     Publication Date:  2007 Feb 
Date Detail:
Created Date:  2006-12-25     Completed Date:  2007-03-16     Revised Date:  2014-09-21    
Medline Journal Info:
Nlm Unique ID:  8503886     Medline TA:  J Hepatol     Country:  England    
Other Details:
Languages:  eng     Pagination:  222-9     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
Apoptosis
Bile Duct Neoplasms / drug therapy*
Cell Line, Tumor
Cholangiocarcinoma / drug therapy*
Deoxycytidine / administration & dosage,  analogs & derivatives
Down-Regulation
Drug Interactions
Fluoresceins / metabolism
Fluorouracil / administration & dosage
Humans
Membrane Transport Proteins / metabolism
Mitomycin / administration & dosage
Multidrug Resistance-Associated Proteins / metabolism
P-Glycoprotein / metabolism
Tannins / therapeutic use*
Grant Support
ID/Acronym/Agency:
DK60637/DK/NIDDK NIH HHS; DK69370/DK/NIDDK NIH HHS; R01 DK069370/DK/NIDDK NIH HHS; R03 DK060637/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Fluoresceins; 0/Membrane Transport Proteins; 0/Multidrug Resistance-Associated Proteins; 0/P-Glycoprotein; 0/Tannins; 0/multidrug resistance-associated protein 1; 0/multidrug resistance-associated protein 2; 0W860991D6/Deoxycytidine; 50SG953SK6/Mitomycin; B76N6SBZ8R/gemcitabine; U3P01618RT/Fluorouracil; V0YM2B16TS/fluorexon
Comments/Corrections

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


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