PMID- 31262888 OWN - NLM STAT- MEDLINE DCOM- 20190708 LR - 20190708 IS - 1791-7530 (Electronic) IS - 0250-7005 (Linking) VI - 39 IP - 7 DP - 2019 Jul TI - Cetrimonium Bromide Inhibits Cell Migration and Invasion of Human Hepatic SK-HEP-1 Cells Through Modulating the Canonical and Non-canonical TGF-beta Signaling Pathways. PG - 3621-3631 LID - 10.21873/anticanres.13510 [doi] AB - 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, beta-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-GSK3beta. Based on these observations, we suggest that CTAB not only inhibits the canonical transforming growth factor-beta (TGF-beta) 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-beta signaling including MAPK pathways like ERK1/2, p38 MAPK, JNK and PI3K. CONCLUSION: CTAB is involved in the suppression of TGF-beta-mediated mesenchymal phenotype and could be a potent medical agent for use in controlling the migration and invasion of hepatic adenocarcinoma. CI - Copyright(c) 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved. FAU - Wu, Tsai-Kun AU - Wu TK AD - Division of Renal Medicine, Tungs' Taichung Metroharbor Hospital, Taichung, Taiwan, R.O.C. AD - Department of Nutrition, Master Program of Biomedical Nutrition, Hungkuang University, Taichung, Taiwan, R.O.C. AD - Department of Nursing, Jen-Teh Junior College of Medicine, Nursing and Management, Miaoli, Taiwan, R.O.C. FAU - Chen, Chung-Hung AU - Chen CH AD - Department of Gastroenterology, Chang Bing Show Chwan Memorial Hospital, Changhua, Taiwan, R.O.C. FAU - Pan, Ying-Ru AU - Pan YR AD - Department of Medical Research, Tungs' Taichung Metroharbor Hospital, Taichung, Taiwan, R.O.C. FAU - Hu, Ching-Wen AU - Hu CW AD - Department of Nursing, Tungs' Taichung Metroharbor Hospital, Taichung, Taiwan, R.O.C. FAU - Huang, Fu-Mei AU - Huang FM AD - Operating Theatre, Chung Shan Medical University Hospital, Taichung, Taiwan, R.O.C. FAU - Liu, Jer-Yuh AU - Liu JY AD - Center for Molecular Medicine, China Medical University Hospital, Taichung, Taiwan, R.O.C. AD - Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan, R.O.C. FAU - Lee, Chia-Jen AU - Lee CJ AD - Department of Medical Research, Tungs' Taichung Metroharbor Hospital, Taichung, Taiwan, R.O.C. chiajenlee54@gmail.com. AD - Department of Rehabilitation, Jen-Teh Junior College of Medicine, Nursing and Management, Miaoli, Taiwan R.O.C. LA - eng PT - Journal Article PL - Greece TA - Anticancer Res JT - Anticancer research JID - 8102988 RN - 0 (Antineoplastic Agents) RN - 0 (Transforming Growth Factor beta) RN - Z7FF1XKL7A (Cetrimonium) SB - IM MH - Adenocarcinoma/drug therapy/*metabolism MH - Antineoplastic Agents/*pharmacology MH - Cell Line, Tumor MH - Cell Movement/drug effects MH - Cetrimonium/*pharmacology MH - Humans MH - Liver Neoplasms/drug therapy/*metabolism MH - Neoplasm Invasiveness MH - Signal Transduction/drug effects MH - Transforming Growth Factor beta/*metabolism OTO - NOTNLM OT - Cetrimonium bromide (CTAB) OT - SK-HEP-1 OT - hepatic cancer OT - transforming growth factor-beta (TGF-beta) EDAT- 2019/07/03 06:00 MHDA- 2019/07/10 06:00 CRDT- 2019/07/03 06:00 PHST- 2019/05/20 00:00 [received] PHST- 2019/06/18 00:00 [revised] PHST- 2019/06/20 00:00 [accepted] PHST- 2019/07/03 06:00 [entrez] PHST- 2019/07/03 06:00 [pubmed] PHST- 2019/07/10 06:00 [medline] AID - 39/7/3621 [pii] AID - 10.21873/anticanres.13510 [doi] PST - ppublish SO - Anticancer Res. 2019 Jul;39(7):3621-3631. doi: 10.21873/anticanres.13510.