β-Eudesmol Inhibits the Migration of Cholangiocarcinoma Cells by Suppressing Epithelial-Mesenchymal Transition via PI3K/AKT and p38MAPK Modulation

Acharya, Bishwanath; Chajaroenkul, Wanna; Na-Bangchang, Kesara

doi:10.31557/APJCP.2022.23.8.2573

β-Eudesmol Inhibits the Migration of Cholangiocarcinoma Cells by Suppressing Epithelial-Mesenchymal Transition via PI3K/AKT and p38MAPK Modulation

Document Type : Research Articles

Authors

¹ Chulabhorn International College of Medicine, Thammasat University, Rangsit Center, Klong Luang, Pathum Thani 12120, Thailand.

² Center of Excellence in Pharmacology and Molecular Biology of Malaria and Cholangiocarcinoma, Chulabhorn International College of Medicine, Thammasat University, Rangsit Center, Klong Luang, Pathum Thani 12120, Thailand.

³ Drug Discovery and Development Center, Thammasat University, Rangsit Center, Klong Luang, Pathum Thani 12120, Thailand.

10.31557/APJCP.2022.23.8.2573

Abstract

Background: Cholangiocarcinoma (CCA) is a highly aggressive tumor with a greater risk of distant metastasis. A drug that prevents CCA development and spread is urgently needed. In this research, we investigated the effect of β-eudesmol on the migration and invasion and epithelial-mesenchymal transformation (EMT) of the CCA cell line. Materials and Methods: MTT and transwell assays were used to investigate the antiproliferative activity, as well as activity on cell migration and cell invasion. Real-time PCR and western blot analysis were used to investigate the expression of EMT marker genes and proteins. Results: β-eudesmol was shown to exhibit potent antiproliferative activity (IC50 92.25-185.67 µM) and to significantly reduce CCA cell migration and invasion (27.3-62.7%). At both mRNA and protein levels, it significantly up-regulated the expression of epithelial marker E-cadherin (3-3.4-fold), while down-regulated the expression of mesenchymal markers-vimentin (0.6-0.8-fold) and snail-1 (0.4-0.6-fold). Furthermore, β-eudesmol inhibited PI3K and AKT phosphorylation (0.5-0.8-fold), while activating p38MAPK activity (1.2-3.6-fold). Conclusion: Altogether, the anti-metastatic activity of β-eudesmol might be due to its suppressive effect on EMT via modulating the PI3K/AKT and p38MAPK signaling cascades.

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