2. Academic Validation
  3. Cetrimonium Bromide Inhibits Cell Migration and Invasion of Human Hepatic SK-HEP-1 Cells Through Modulating the Canonical and Non-canonical TGF-β Signaling Pathways

Cetrimonium Bromide Inhibits Cell Migration and Invasion of Human Hepatic SK-HEP-1 Cells Through Modulating the Canonical and Non-canonical TGF-β Signaling Pathways

  • Anticancer Res. 2019 Jul;39(7):3621-3631. doi: 10.21873/anticanres.13510.
Tsai-Kun Wu 1 2 3,  Chung-Hung Chen 4,  Ying-Ru Pan 5,  Ching-Wen Hu 6,  Fu-Mei Huang 7,  Jer-Yuh Liu 8 9,  Chia-Jen Lee 10 11
Affiliations

Affiliations

  • 1 Division of Renal Medicine, Tungs' Taichung Metroharbor Hospital, Taichung, Taiwan, R.O.C.
  • 2 Department of Nutrition, Master Program of Biomedical Nutrition, Hungkuang University, Taichung, Taiwan, R.O.C.
  • 3 Department of Nursing, Jen-Teh Junior College of Medicine, Nursing and Management, Miaoli, Taiwan, R.O.C.
  • 4 Department of Gastroenterology, Chang Bing Show Chwan Memorial Hospital, Changhua, Taiwan, R.O.C.
  • 5 Department of Medical Research, Tungs' Taichung Metroharbor Hospital, Taichung, Taiwan, R.O.C.
  • 6 Department of Nursing, Tungs' Taichung Metroharbor Hospital, Taichung, Taiwan, R.O.C.
  • 7 Operating Theatre, Chung Shan Medical University Hospital, Taichung, Taiwan, R.O.C.
  • 8 Center for Molecular Medicine, China Medical University Hospital, Taichung, Taiwan, R.O.C.
  • 9 Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan, R.O.C.
  • 10 Department of Medical Research, Tungs' Taichung Metroharbor Hospital, Taichung, Taiwan, R.O.C. chiajenlee54@gmail.com.
  • 11 Department of Rehabilitation, Jen-Teh Junior College of Medicine, Nursing and Management, Miaoli, Taiwan R.O.C.
PMID: 31262888 DOI: 10.21873/anticanres.13510
Abstract

Background/aim: Cetrimonium bromide (CTAB), a quaternary ammonium surfactant, is an antiseptic agent against bacteria and fungi. However, the mechanisms by which its pharmacological actions affect epithelial-mesenchymal transition (EMT) in hepatocellular carcinoma (HCC) cells, such as adenocarcinoma in SK-HEP-1 cells, have not been investigated. We, thereby, investigated whether CTAB inhibits cellular mobility and invasiveness of human hepatic adenocarcinoma in SK-HEP-1 cells.

Materials and methods: SK-HEP-1 cells were treated with CTAB, and subsequent migration and invasion were measured by wound healing and transwell assays. Protein expression was detected by immunoblotting analysis.

Results: Our data revealed that treatment of SK-HEP-1 cells with CTAB altered their mesenchymal spindle-like morphology. CTAB exerted inhibitory effects on the migration and invasion of SK-HEP-1 cells dose-dependently, and reduced protein levels of matrix metalloproteinase-2 (MMP-2), MMP-9, snail, slug, twist, vimentin, fibronectin, N-Cadherin, SMAD2, SMAD3, SMAD4, phosphoinositide-3-kinase (PI3K), p-PI3K, Akt, p-Akt, β-catenin, mammalian target of rapamycin (mTOR), p-mTOR, p-p70S6K, p-extracellular signal-regulated kinases (ERK)1/2, p-p38 mitogen-activated protein kinase (MAPK) and p-c-Jun N-terminal kinase (JNK), but increased protein levels of tissue inhibitor matrix metalloproteinase-1 (TIMP-1), TIMP-2, claudin-1 and p-GSK3β. Based on these observations, we suggest that CTAB not only inhibits the canonical Transforming Growth Factor-β (TGF-β) signaling pathway though reducing SMADs (an acronym from the fusion of Caenorhabditis elegans Sma genes and the Drosophila Mad, Mothers against decapentaplegic proteins), but also restrains the non-canonical TGF-β signaling including MAPK pathways like ERK1/2, p38 MAPK, JNK and PI3K.

Conclusion: CTAB is involved in the suppression of TGF-β-mediated mesenchymal phenotype and could be a potent medical agent for use in controlling the migration and invasion of hepatic adenocarcinoma.

Keywords

Cetrimonium bromide (CTAB); SK-HEP-1; hepatic cancer; transforming growth factor-β (TGF-β).

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