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Year : 2022  |  Volume : 18  |  Issue : 79  |  Page : 729-737

Induction of cell death and apoptosis of Oroxylum Indicum extract with gemcitabine on human cholangiocarcinoma cells through reducing epidermal growth factor receptor

1 Department of Pharmacology, Faculty of Medicine; Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand
2 Faculty of Medicine, Biomedical Sciences Research Unit, Mahasarakham University, Muang District, Maha Sarakham, Thailand

Correspondence Address:
Benjaporn Buranrat
Faculty of Medicine, Mahasarakham University, Talad, Muang, Maha Sarakham – 44000
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/pm.pm_133_22

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Background: Cholangiocarcinoma (CCA), epithelial bile duct cancer, is deadly cancer with a very poor prognosis and standard anticancer drugs strategy remains poor and unfavorable outcomes. Objectives: In this study, we examined how Oroxylum indicum leaf extract in combination with gemcitabine (anticancer drug) affects the viability, apoptosis, and migration of CCA cells. Materials and Methods: Two CCA cells, KKU-100 and KKU-M452, were incubated with O. indicum or gemcitabine or in combination for 24-72 hr and these effects were explored by using the sulforhodamine B, colony formation, cell cycle arrest, ROS formation, mitochondrial function, migration, and Western blot analysis. Results: O. indicum expressively suppressed the growth of both CCA cells at 72 hr with IC50 values were 9.88 ± 1.36 and 8.56 ± 1.02 μg/mL for KKU-100 and KKU-M452 cells, with the number of cells were decreased by dose-dependent manner. Further, the extract caused the reduction of colony formation and then suppressed the cells at G0/G1 phase for KKU-100 and S to G2/M phase for KKU-M452 cells. At 250 μg/mL, two CCA cells generated ROS formation along with decreasing mitochondrial function and then led to induce cancer cells apoptosis. Furthermore, O. indicum extract inhibited CCA cell migration via decreasing MMP-9 expression levels. The mechanism of its action was significant suppressed EGFR and caspase 3 levels. Combination group of O. indicum plus gemcitabine found that O. indicum potentiated gemcitabine to inhibit cell viability, induce apoptosis, increase ROS formation, decrease mitochondrial function, and suppress EGFR expression. Conclusion: O. indicum leaf extracts with potentiation of gemcitabine can reduce CCA cell growth, induce apoptosis, and cell migration through decreasing EGFR and caspase 3 expression. O. indicum could be useful for enhancing the activity of anticancer drugs displayed to prevent or treat CCA.

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