13‑cis‑retinoic acid inhibits the self‑renewal, migration, invasion and adhesion of cholangiocarcinoma cells

Sep 28, 2026

Uploaded by dhado

13‑cis‑retinoic acid (13CRA), an FDA‑approved drug for severe acne, is evaluated for anti‑cancer potential in cholangiocarcinoma (CCA), where effective therapies for metastatic disease remain limited. The study tests 13CRA effects on CCA cell self‑renewal, migration, invasion, and adhesion, and examines underlying mechanisms. 13CRA suppresses proliferation by inhibiting self‑renewal, induces G2/M cell‑cycle arrest through regulation of cell‑cycle genes and proteins, and reduces migration, invasion, and adhesion by modulating EMT, invasion, and adhesion‑associated gene and protein networks.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages17

Reading Time43 min

AccessFree to download

Abstract

Introduction

Background on 13‑cis‑retinoic acid (13CRA)

Clinical challenge in cholangiocarcinoma (CCA)

Focus on cancer hallmarks: proliferation, EMT, stemness, plasticity

INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE 51: 20, 2023 13‑cis‑retinoic acid inhibits the self‑renewal, migration, invasion and adhesion of cholangiocarcinoma cells SIRIWOOT BUTSRI, VEERAPOLKUKONGVIRIYAPAN, LADDAWAN SENGGUNPRAI, SARINYA KONGPETCH and AUEMDUAN PRAWAN Department of Pharmacology, Faculty of Medicine, Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen 40002, Thailand Received October 20, 2021; Accepted January 3, 2023 DOI: 10.3892/ijmm.2023.5223 Abstract. 13‑cis‑retinoic acid (13CRA), a Food and Drug Administration‑approved drug for severe acne, is currently being investigated for its potential use in skin cancer preven‑ tion. 13CRA has been reported to exhibit antitumor effects against various types of cancer cells, both in vitro and in vivo. However, to the best of our knowledge, no information is yet available regarding the effects of 13CRA on cholangio‑ carcinoma (CCA), a malignancy of the bile duct epithelia . Currently, there are no reliably effective therapeutic options for metastatic CCA. The present study thus aimed to evaluate the effects of 13CRA on the self‑renewal, migration, invasion and adhesion of CCA cells, and also investigated the underlying mechanisms. The results revealed that 13CRA suppressed cell proliferation via the inhibition of the self‑renewal ability of CCA cells. 13CRA induced cell cycle arrest at the G2/M phase in KKU‑100 and KKU‑213B CCA cells through the regulation of cell cycle‑regulatory genes and proteins. 13CRA reduced the cell migratory ability of both cell lines via the modulation of the genes and proteins associated with epithelial‑mesen‑ chymal transition . 13CRA also inhibited the invasive and adhesive abilities of CCA cells via the suppression of genes and proteins associated with the invasion and adhesion of CCA cells. On the whole, these results suggested that 13CRA exerts suppressive effects on CCA cell proliferation, migration, adhesion and invasion. Introduction 13‑cis‑retinoic acid (13CRA), a member of the family of vitamin A compounds (1), plays a role in several cellular processes, Correspondence to: Dr Auemduan Prawan, Department of Pharmacology, Faculty of Medicine, Cholangiocarcinoma Research Institute, Khon Kaen University, 123 Mittraparp Highway, Muang, Khon Kaen 40002, Thailand E‑[mail: peuamd@kku.ac.th](mail: peuamd@kku.ac.th) Key words: 13‑cis‑retinoic acid, cholangiocarcinoma, proliferation, migration, invasion, epithelial‑mesenchymal transition such as cell proliferation, differentiation and apoptosis (2) . At present, 13CRA, a Food and Drug Administration‑approved drug for severe acne, is a readily available and well‑tolerated agent that has been reported to exhibit antitumor potential both in vitro and in vivo in various types of cancer (3‑8) . Previous preclinical studies have demonstrated that 13CRA inhibits the proliferation of cancer cells, including small‑cell lung, gastric and breast cancer cells (4‑6) . In addition, 13CRA induces apoptosis and exerts a suppressive effect on the metastasis of melanoma and colon cancer (7,8) . 13CRA has been investigated for its anticancer activity for several years, and its potential mechanisms of action have been explored in various cancer types; however, to the best of our knowledge, there is no report available to date on the anticancer activity and potential use of 13CRA in cholangiocarcinoma (CCA) . Thus, information on the roles of 13CRA in CCA cells may provide critical, useful evidence for further studies. CCA is an aggressive tumor with a poor prognosis due to its late clinical presentation and lack of effective non‑surgical therapies (9) . Several risk factors for CCA have been identi‑ fied, including primary sclerosing cholangitis, hepatobiliary parasites, hepatolithiasis, Caroli disease, choledochal cystsand Thorotrast (10) . In Asia, CCA is associated with chronic infection with the liver flukes Opisthorchis viverrini and Clonorchis sinensis , which is a

FAQs

What aims does the study address for 13‑cis‑retinoic acid in cholangiocarcinoma?

It evaluates how 13CRA affects CCA cell self‑renewal, migration, invasion, and adhesion, and investigates the mechanisms behind these effects.

How does 13‑cis‑retinoic acid suppress cholangiocarcinoma cell growth?

The results indicate 13CRA suppresses cell proliferation by inhibiting the self‑renewal ability of CCA cells and by inducing G2/M cell‑cycle arrest through regulation of cell‑cycle genes and proteins.

Which molecular processes are implicated in the effects on migration, invasion, and adhesion?

13CRA reduces migratory ability via modulation of genes and proteins linked to epithelial‑mesenchymal transition, and it inhibits invasive and adhesive abilities by suppressing genes and proteins associated with invasion and adhesion in CCA cells.

Sep 28, 2026

Uploaded by dhado