title: Saturated fatty acid induces cancer stem cell-like properties in human hepatoma cells.
abstract: Hepatic steatosis has been reported to be a risk factor for the development of liver cancer. The underlying mechanism for carcinogenesis remains to be elucidated. It has been postulated that cancer stem cells (CSCs) within tumor tissues are a subset of cells with stem cell properties of self-renewal and undifferentiation. The purpose of this study was to investigate the effects of a saturated fatty acid, palmitate (PA), on CSC-like properties of human hepatoma HepG2 cells. We investigated the effects of PA on HepG2 cells and primary rat hepatocytes (PRH) by exposing them to PA to induce lipid accumulation. Significant fat accumulation was observed by Oil Red O staining in cells exposed to PA, and it was accompanied by significant increase in NFκB (p65) nuclear translocation in HepG2 cells. Notably, PA significantly enhanced the sphere forming ability of HepG2 cells, but not PRH. Furthermore, PA significantly increased stemness gene expressions of Sox2 and Oct4, and sonic hedgehog (Shh) production. Notably, NFκB inhibitors, N-Acetyl-L-cysteine and pyrollidine dithiocarbamate, and a NOX inhibitor, diphenyleneiodonium, significantly attenuated PA-induced sphere forming ability of HepG2 cells. Our results suggest that lipid accumulation may not only induce pro-inflammatory responses in hepatocytes but may also activate CSC-like properties of hepatoma cells through NFκB activation.
authors.affiliation: Shin Kong Wu Ho&mdash;Su Memorial Hospital Division of Hepatology and Gastroenterology, Department of Internal Medicine Taipei Taiwan.
authors.forename: L-W
authors.initials: LW
authors.lastname: Chong
authors.affiliation: China Medical University Graduate Institute of Cancer Biology and Center for Molecular Medicine Taichung Taiwan.
authors.forename: R-H
authors.initials: RH
authors.lastname: Chou
authors.affiliation: National Yang&mdash;Ming University Proteomics Research Center Taipei Taiwan.
authors.forename: C-C
authors.initials: CC
authors.lastname: Liao
authors.affiliation: National Yang Ming University Institute of Clinical Medicine, School of Medicine Taipei Taiwan.
authors.forename: T-F
authors.initials: TF
authors.lastname: Lee
authors.affiliation: Shin Kong Wu Ho&mdash;Su Memorial Hospital Division of Hepatology and Gastroenterology, Department of Internal Medicine Taipei Taiwan.
authors.forename: Y
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Shin Kong Wu Ho&mdash;Su Memorial Hospital Division of Hepatology and Gastroenterology, Department of Internal Medicine Taipei Taiwan.
authors.forename: K-C
authors.initials: KC
authors.lastname: Yang
authors.affiliation: Mackay Medical College Institute of Biomedical Sciences New Taipei City Taiwan hsuyc&commat;mmc.edu.tw.
authors.forename: Y-C
authors.initials: YC
authors.lastname: Hsu
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007249:Inflammation / Q000473:pathology; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology; D008297:Male; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D065626:Non-alcoholic Fatty Liver Disease / Q000378:metabolism* / Q000473:pathology; D010168:Palmitates / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D051996:Transcription Factor RelA / Q000378:metabolism
chemical_list: D010168:Palmitates; D051996:Transcription Factor RelA