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

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 (IC 50 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.

Investigation of Fibroblast Growth Factor Peptide Antagonist on Mouse Model Breast Tumor through ERK/MAPK and PI3K/AKT Signaling Pathways

“…Peptide can affect the signal transduction pathways, including phosphoinositide 3-kinase (PI3K) and AKT (protein kinase B), and subsequently, the proliferation, differentiation, apoptosis, and metastasis processes [11][12][13]. Using different peptides that alter PI3K/AKT signaling pathways in cell lines for different cancers including Cholangiocarcinoma and melanoma were introduced earlier [14,15].…”

Modulatory Effects of Atractylodin and β-Eudesmol on Human Cytochrome P450 Enzymes: Potential Drug-Drug Interactions

“…Both are the primary active ingredients responsible for the majority of the pharmacologic properties of AL [ 6 ]. Recently, promising activities against cholangiocarcinoma of atractylodin and β-eudesmol have been demonstrated in a series of non-clinical studies [ 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 ]. With regard to metabolic drug interactions, the crude ethanolic extract of AL rhizomes was shown to potently inhibit human CYP1A2 in vitro, with comparable potency with the reference hCYP1A2 inhibitor—α-naphthoflavone.…”

Regulation of Epithelial-Mesenchymal Transition by Cyrtopodion Scabrum: An in vitro Study against Colorectal Cancer Cells

“…It has been proposed that Epithelial-Mesenchymal Transition (EMT) might be closely related to the acquisition of invasive traits by tumor cells, thereby triggering the dissemination of carcinoma cells and subsequent metastasis (Kamal et al, 2022;Tsai and Yang, 2013). EMT is a process during which the epithelial cells lose their epithelial features such as cellcell adhesion and phenotypic characteristics and instead acquire mesenchymal traits such as increased mobility (Acharya et al, 2022). This transition is characterized by changes in the expression pattern of specific genes known as EMT markers including N-cadherin and Snail (mesenchymal marker), and E-cadherin (epithelial marker) (Riggi et al, 2018).…”