title: Corilagin suppresses cholangiocarcinoma progression through Notch signaling pathway in vitro and in vivo.
abstract: 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.
authors.affiliation: Medical College of Xiamen University, Xiamen, Fujian, P.R. China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Gu
authors.affiliation: Medical College of Xiamen University, Xiamen, Fujian, P.R. China.
authors.forename: Linfeng
authors.initials: L
authors.lastname: Xiao
authors.affiliation: The Research and Development Center for Medicine Plants and Plant Drugs, Xiamen Overseas Chinese Subtropical Plant Introduction Garden, Xiamen, Fujian, P.R. China.
authors.forename: Yanlin
authors.initials: Y
authors.lastname: Ming
authors.affiliation: The Research and Development Center for Medicine Plants and Plant Drugs, Xiamen Overseas Chinese Subtropical Plant Introduction Garden, Xiamen, Fujian, P.R. China.
authors.forename: Zhizhong
authors.initials: Z
authors.lastname: Zheng
authors.affiliation: Medical College of Xiamen University, Xiamen, Fujian, P.R. China.
authors.forename: Wengang
authors.initials: W
authors.lastname: Li
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D001650:Bile Duct Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D018281:Cholangiocarcinoma / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005960:Glucosides / Q000008:administration & dosage* / Q000494:pharmacology; D006801:Humans; D047348:Hydrolyzable Tannins / Q000008:administration & dosage* / Q000494:pharmacology; D066298:In Vitro Techniques; D051379:Mice; D008819:Mice, Nude; D051880:Receptors, Notch / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D000072056:Transcription Factor HES-1 / Q000235:genetics; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D005960:Glucosides; D047348:Hydrolyzable Tannins; D051880:Receptors, Notch; D000072056:Transcription Factor HES-1; C078493:HES1 protein, human; C049096:corilagin