Cetyltrimethylammonium Bromide Disrupts the Mesenchymal Characteristics of HA22T/VGH Cells Via Inactivation of c-Met/PI3K/Akt/mTOR Pathway

Anticancer Res. 2020 Aug;40(8):4513-4522. doi: 10.21873/anticanres.14456.

Abstract

Background/aim: Hepatocellular carcinoma (HCC) arises from hepatocytes, and is the most frequently occurring malignancy of primary liver cancer. In this study, we investigated the anti-metastatic effects of the quaternary ammonium compound, cetyltrimethylammonium bromide (CTAB), on HA22T/VGH HCC cells.

Materials and methods: According to our preliminary data, the effect of CTAB on cell cycle distribution, migration, invasion and the associated protein levels was examined using flow cytometry, wound-healing migration, Matrigel transwell invasion assay and western blotting under sub-lethal concentrations.

Results: CTAB treatment of HA22T/VGH cells casued dose-dependent mesenchymal-epithelial transition (MET)-like changes and impaired migration and invasion capabilities. In addition, CTAB reduced the levels of metastasis-related proteins including c-Met, phosphoinositide 3-kinase (PI3K), Akt, mammalian target of rapamycin (mTOR), ribosomal protein S6 kinase (p70S6K), Twist, N-cadherin, and Vimentin. Moreover, pretreatment with hepatocyte growth factor (HGF) rescued CTAB-mediated effects.

Conclusion: CTAB exhibited potent anti-EMT and anti-metastatic activities through the inhibition of migration and invasion of HA22T/VGH cells. CTAB interrupted the mesenchymal characteristics of HA22T/VGH cells, which were significantly alleviated by HGF in a dose-dependent manner. CTAB has the potential to evolve as a therapeutic agent for HCC.

Keywords: Cetyltrimethylammonium bromide (CTAB); HA22T/VGH; hepatic cancer; mesenchymal to epithelial transition.

MeSH terms

  • Carcinoma, Hepatocellular / drug therapy
  • Carcinoma, Hepatocellular / metabolism*
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Survival / drug effects
  • Cetrimonium / pharmacology*
  • Dose-Response Relationship, Drug
  • Epithelial-Mesenchymal Transition / drug effects*
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Liver Neoplasms / drug therapy
  • Liver Neoplasms / metabolism*
  • Male
  • Middle Aged
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Proto-Oncogene Proteins c-met / metabolism
  • Signal Transduction / drug effects*
  • TOR Serine-Threonine Kinases / metabolism

Substances

  • MTOR protein, human
  • MET protein, human
  • Proto-Oncogene Proteins c-met
  • AKT1 protein, human
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases
  • Cetrimonium