Arctigenin inhibits cholangiocarcinoma progression by regulating cell migration and cell viability via the N-cadherin and apoptosis pathway
- 20 July 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in Naunyn-Schmiedebergs Archiv für experimentelle Pathologie und Pharmakologie
- Vol. 394 (10), 2049-2059
- https://doi.org/10.1007/s00210-021-02123-0
Abstract
Northeast Thailand has the highest incidence of cholangiocarcinoma (CCA) in the world. The lack of promising diagnostic markers and appropriate therapeutic drugs is the main problem for metastatic stage CCA patients who have a poor prognosis. N-cadherin, a cell adhesion molecule, is usually upregulated in cancers and has been proposed as an important mediator in epithelial-mesenchymal transition (EMT), one of the metastasis processes. Additionally, it has been shown that arctigenin, a seed isolated compound from Arctium lappa, can inhibit cancer cell progression via suppression of N-cadherin pathway. In this study, we investigated the protein expression of N-cadherin and its correlation with clinicopathological data of CCA patients, as well as the impact of arctigenin on KKU-213A and KKU-100 CCA cell lines and its underlying mechanisms. Immunohistochemistry results demonstrated that high expression of N-cadherin was significantly associated with severe CCA stage (p = 0.027), and shorter survival time (p = 0.002) of CCA patients. The mean overall survival times between low and high expression of N-cadherin were 31.6 and 14.8 months, respectively. Wound healing assays showed that arctigenin significantly inhibited CCA cell migration by downregulating N-cadherin whereas upregulating E-cadherin expression. Immunocytochemical staining revealed that arctigenin suppressed the expression of N-cadherin in both CCA cell lines. Furthermore, flow cytometry and western blot analysis revealed that arctigenin significantly reduced CCA cell viability and induced apoptosis via the Bax/Bcl-2/caspase-3 pathway. This research supports the use of N-cadherin as a prognostic marker for CCA and arctigenin as a potential alternative therapy for improving CCA treatment outcomes.Keywords
Funding Information
- The Program Management Unit for Human Resources & Institutional Development, Research and Innovation (B05F630053)
- Khon Kaen University grant (KKU63)
This publication has 51 references indexed in Scilit:
- Vascular Endothelial Growth Factor Receptor-1 Activation Promotes Migration and Invasion of Breast Cancer Cells through Epithelial-Mesenchymal TransitionPLOS ONE, 2013
- Linking Metabolic Abnormalities to Apoptotic Pathways in Beta Cells in Type 2 DiabetesCells, 2013
- Prognostic Significance of Twist and N-Cadherin Expression in NSCLCPLOS ONE, 2013
- Gemcitabine alone or in combination with cisplatin in patients with biliary tract cancer: a comparative multicentre study in JapanBritish Journal of Cancer, 2010
- The basics of epithelial-mesenchymal transitionJCI Insight, 2009
- Advances in diagnosis, treatment and palliation of cholangiocarcinoma: 1990-2009World Journal of Gastroenterology, 2009
- A Switch from E-Cadherin to N-Cadherin Expression Indicates Epithelial to Mesenchymal Transition and Is of Strong and Independent Importance for the Progress of Prostate CancerClinical Cancer Research, 2007
- N-Cadherin as a Novel Prognostic Marker of Progression in Superficial Urothelial TumorsClinical Cancer Research, 2006
- N-Cadherin Expression and Epithelial-Mesenchymal Transition in Pancreatic CarcinomaClinical Cancer Research, 2004
- A "quickscore" method for immunohistochemical semiquantitation: validation for oestrogen receptor in breast carcinomas.Journal of Clinical Pathology, 1995