Objective: Cholangiocarcinoma (CCA) is a malignant tumor with aggressive metastatic property resulted from dysregulation of metastasis-regulated signaling pathways. The aim of this study was to investigate the effect of cucurbitacin B on metastatic behavior of CCA cells through modulation of focal adhesion kinase (FAK) protein. Methods: KKU-452 cells were treated with a specific FAK inhibitor, FAK inhibitor-14, or cucurbitacin B at various concentrations for 24 h. Cell viability was assessed by sulforhodamine B assay. The migratory and invasive abilities of the cells were investigated using wound healing and transwell invasion assays, respectively. The fibronectin-coated plate was used for adhesion assay. The effects of the test compounds on FAK activation and the expression of metastasis-associated proteins were determined by Western blot analysis. The amount of MMP-9 was evaluated using a commercial ELISA Kit. Results: FAK inhibitor-14 and cucurbitacin B at concentrations which minimally affected KKU-452 cell viability could suppress FAK activation, evidently by decreased level of phospho-FAK protein after exposure to the compound. At these conditions, cucurbitacin B suppressed metastatic behavior including migration, invasion and adhesion abilities of CCA cells similar to FAK inhibitor-14. Further molecular studies demonstrated that FAK inhibitor-14 and cucurbitacin B downregulated the expression of metastasis-associated proteins including MMP-9, ICAM-1 and VEGF. Consequently, exposure to cucurbitacin B inhibited the production of MMP-9 enzyme in CCA cells similar to FAK inhibitor-14 treatment. Conclusion: FAK participated in regulation of metastatic behavior of KKU-452 CCA cells. Cucurbitacin B suppressed FAK activation in the cells which was associated with inhibition of metastasis essential steps and their related metastatic proteins. The compound may be developed as a novel therapeutic agent for CCA metastasis therapy.
Kaewmeesri, P., Kukongviriyapan, V., Prawan, A., Kongpetch, S., & Senggunprai, L. (2021). Cucurbitacin B Diminishes Metastatic Behavior of Cholangiocarcinoma Cells by Suppressing Focal Adhesion Kinase. Asian Pacific Journal of Cancer Prevention, 22(1), 219-225. doi: 10.31557/APJCP.2021.22.1.219
MLA
Putthaporn Kaewmeesri; Veerapol Kukongviriyapan; Auemduan Prawan; Sarinya Kongpetch; Laddawan Senggunprai. "Cucurbitacin B Diminishes Metastatic Behavior of Cholangiocarcinoma Cells by Suppressing Focal Adhesion Kinase". Asian Pacific Journal of Cancer Prevention, 22, 1, 2021, 219-225. doi: 10.31557/APJCP.2021.22.1.219
HARVARD
Kaewmeesri, P., Kukongviriyapan, V., Prawan, A., Kongpetch, S., Senggunprai, L. (2021). 'Cucurbitacin B Diminishes Metastatic Behavior of Cholangiocarcinoma Cells by Suppressing Focal Adhesion Kinase', Asian Pacific Journal of Cancer Prevention, 22(1), pp. 219-225. doi: 10.31557/APJCP.2021.22.1.219
VANCOUVER
Kaewmeesri, P., Kukongviriyapan, V., Prawan, A., Kongpetch, S., Senggunprai, L. Cucurbitacin B Diminishes Metastatic Behavior of Cholangiocarcinoma Cells by Suppressing Focal Adhesion Kinase. Asian Pacific Journal of Cancer Prevention, 2021; 22(1): 219-225. doi: 10.31557/APJCP.2021.22.1.219
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