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.
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: S D Taylor-Robinson; M B Toledano; S Arora; T J Keegan; S Hargreaves; A Beck; S A Khan; P Elliott; H C Thomas Journal: Gut Date: 2001-06 Impact factor: 23.059
Authors: Shahid A Khan; Simon D Taylor-Robinson; Mireille B Toledano; Angus Beck; Paul Elliott; Howard C Thomas Journal: J Hepatol Date: 2002-12 Impact factor: 25.083
Authors: A M Bergman; H M Pinedo; I Talianidis; G Veerman; W J P Loves; C L van der Wilt; G J Peters Journal: Br J Cancer Date: 2003-06-16 Impact factor: 7.640
Authors: Elham Hatami; Prashanth K B Nagesh; Mohammed Sikander; Anupam Dhasmana; Subhash C Chauhan; Meena Jaggi; Murali M Yallapu Journal: ACS Omega Date: 2022-06-28