Tannic acid synergizes the cytotoxicity of chemotherapeutic drugs in human cholangiocarcinoma by modulating drug efflux pathways
| Autor: | Hania Wehbe, Roger Henson, Fanyin Meng, Tushar Patel, Peter J. Naus, Grant Bleeker |
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| Rok vydání: | 2006 |
| Předmět: |
Mitomycin
Down-Regulation Apoptosis macromolecular substances Pharmacology Deoxycytidine Article Cholangiocarcinoma chemistry.chemical_compound Cell Line Tumor Tannic acid Antineoplastic Combined Chemotherapy Protocols Humans Drug Interactions Gallic acid ATP Binding Cassette Transporter Subfamily B Member 1 Cytotoxicity P-glycoprotein Hepatology biology Mitomycin C Membrane Transport Proteins Fluoresceins Gemcitabine Multidrug Resistance-Associated Protein 2 Calcein chemistry Biochemistry Bile Duct Neoplasms Polyphenol biology.protein Efflux Fluorouracil Multidrug Resistance-Associated Proteins Tannins |
| Zdroj: | Journal of hepatology. 46(2) |
| ISSN: | 0168-8278 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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