Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Alendronate blocks human cholangiocarcinoma cell proliferation and migration

Benjaporn Buranrat¹ , Auemduan Prawan^2,3, Laddawan Senggunprai^2,3, Veerapol Kukongviriyapan^2,3

¹Faculty of Medicine, Biomedical Science Research Unit, Mahasarakham University, Muang District, Maha Sarakham 44000; ²Department of Pharmacology; ³Liver Fluke and Cholangiocarcinoma Research Center, Khon Kaen University, Khon Kaen 40002, Thailand.

For correspondence:- Benjaporn Buranrat Email: benjaporn.b@msu.ac.th

Accepted: 27 May 2019 Published: 30 June 2019

Citation: Buranrat B, Prawan A, Senggunprai L, Kukongviriyapan V. Alendronate blocks human cholangiocarcinoma cell proliferation and migration. Trop J Pharm Res 2019; 18(6):1179-1184 doi: 10.4314/tjpr.v18i6.5

© 2019 The authors.
This is an Open Access article that uses a funding model which does not charge readers or their institutions for access and distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0) and the Budapest Open Access Initiative (http://www.budapestopenaccessinitiative.org/read), which permit unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited..

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.

Keywords: Alendronate, Cholangiocarcinoma, Mevalonate (MVA), Cell death, Matrix metallopeptidase (MMP), Bisphosphonates