Corilagin suppresses cholangiocarcinoma progression through Notch signaling pathway in vitro and in vivo

Int J Oncol. 2016 May;48(5):1868-76. doi: 10.3892/ijo.2016.3413. Epub 2016 Mar 2.


Corilagin is a natural plant polyphenol tannic acid with antitumor, anti-inflammatory, and anti-oxidative properties. However, the mechanisms of its actions are largely unknown. Our group reported that corilagin could induce cell inhibition in human breast cancer cell line MCF-7 and human liver hepatocellular carcinoma cell lines HepG2. We report here that corilagin inhibits cholangiocarcinoma (CCA) development through regulating Notch signaling pathway. We found that, in vitro, corilagin inhibited CCA cell proliferation, migration and invasion, promoted CCA cell apoptosis, and inhibited Notch1 and Notch signaling pathway protein expression. Co-immunoprecipitation was used to establish Notch intracellular domain (NICD) interaction with MAML1 and P300 in CCA. Importantly, corilagin reduced Hes1 mRNA level through inhibiting Hes1 promoter activity. In nude mice, corilagin inhibited CCA growth and repressed the expression of Notch1 and mTOR. These results indicate that corilagin may control CCA cell growth by downregulating the expression of Notch1. Therefore, our findings suggest that corilagin may have the potential to become a new therapeutic drug for human CCA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / pharmacology
  • Bile Duct Neoplasms / drug therapy*
  • Bile Duct Neoplasms / genetics
  • Bile Duct Neoplasms / metabolism
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Cholangiocarcinoma / drug therapy*
  • Cholangiocarcinoma / genetics
  • Cholangiocarcinoma / metabolism
  • Disease Progression
  • Gene Expression Regulation, Neoplastic / drug effects
  • Glucosides / administration & dosage*
  • Glucosides / pharmacology
  • Humans
  • Hydrolyzable Tannins / administration & dosage*
  • Hydrolyzable Tannins / pharmacology
  • In Vitro Techniques
  • Mice
  • Mice, Nude
  • Receptors, Notch / metabolism*
  • Signal Transduction / drug effects
  • Transcription Factor HES-1 / genetics
  • Xenograft Model Antitumor Assays


  • Antineoplastic Agents
  • Glucosides
  • Hydrolyzable Tannins
  • Receptors, Notch
  • Transcription Factor HES-1
  • HES1 protein, human
  • corilagin