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- Title
Alendronate blocks human cholangiocarcinoma cell proliferation and migration.
- Authors
Benjaporn Buranrat; Auemduan Prawan; Laddawan Senggunprai; Veerapol Kukongviriyapan
- Abstract
Purpose: To explore the effect of alendronate on cell death and migration of cholangiocarcinoma (CCA). Methods: Migration and cell death of CCA cells were determined using sulforhodamine B (SRB), colony formation, wound healing, and gelatin zymography assays. The mechanism of action of alendronate was studied with reverse-transcriptase polymerase reaction (RT-PCR) for gene expression and by Western blotting analysis for protein expression. Results: Alendronate stimulated KKU-100 cell death in dose- and time-dependent manner, with low IC50 value, and significantly inhbited colony formation at doses of 5 - 100 µM. Moreover, alendronate at doses of 250 - 1000 µM significantly stimulated CCA apoptosis via reactive oxygen species (ROS) generation, and enhanced caspase 3 activity at a dose of 1000 µM. Moreover, at a dose of 250 µM, it significantly inhibited cell growth through induction of caspase 3 and p53, and reduction of protein expression levels of NF-ĸB. Furthemore, alendronate altered mevalonate (MVA) pathway via downregulation of Rac1 protein expression. In contrast, it significantly inhibited CCA cell migration, and reduced MMP 2 and MMP 9 levels at doses of 25 - 100 µM. Conclusion: Alendronate may be useful as a novel drug for prevention and chemotherapy of CCA.
- Subjects
CELL migration; ALENDRONATE; CELL proliferation; WESTERN immunoblotting; CELL death
- Publication
Tropical Journal of Pharmaceutical Research, 2019, Vol 18, Issue 6, p1179
- ISSN
1596-5996
- Publication type
Article
- DOI
10.4314/tjpr.v18i6.5