Alendronate blocks human cholangiocarcinoma cell proliferation and migration

  • Benjaporn Buranrat
  • Auemduan Prawan
  • Laddawan Senggunprai
  • Veerapol Kukongviriyapan
Keywords: Alendronate, Cholangiocarcinoma, Mevalonate (MVA), Cell death, Matrix metallopeptidase (MMP), Bisphosphonates

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.

Published
2021-05-27
Section
Articles

Journal Identifiers


eISSN: 1596-9827
print ISSN: 1596-5996