title: Genistein inhibits tumor invasion by suppressing multiple signal transduction pathways in human hepatocellular carcinoma cells.
abstract: BACKGROUND
  Genistein (Gen) exhibits anti-mutagenic and anti-metastatic activities in hepatoma cell lines. Gen has suppressive effects on tumor growth and angiogenesis in nude mice. Gen suppresses the enzymatic activity of matrix metalloproteinase (MMP)-9; however, the mechanism underlying its anti-invasive activity on hepatocellular carcinoma (HCC) cells is unclear.
  
  
  METHODS
  In this study, the possible mechanisms underlying Gen-mediated reduction of 12-O-Tetradecanoylphorbol-13-acetate (TPA)-induced cell invasion and inhibition of secreted and cytosolic MMP-9 production in human hepatoma cells (HepG2, Huh-7, and HA22T) and murine embryonic liver cells (BNL CL2) were investigated.
  
  
  RESULTS
  Gen suppressed MMP-9 transcription by inhibiting activator protein (AP)-1 and nuclear factor-κ B (NF-κB) activity. Gen suppressed TPA-induced AP-1 activity through inhibitory phosphorylation of extracellular signal-related kinase (ERK) and c-Jun N-terminal kinase (JNK) signaling pathways, and TPA-stimulated inhibition of NF-κB nuclear translocation through IκB inhibitory signaling pathways. Moreover, Gen suppressed TPA-induced activation of ERK/phosphatidylinositol 3-kinase/Akt upstream of NF-κB and AP-1.
  
  
  CONCLUSIONS
  Gen and its inhibition of multiple signal transduction pathways can control the invasiveness and metastatic potential of HCC.
authors.forename: Shulhn-Der
authors.initials: SD
authors.lastname: Wang
authors.forename: Bor-Chyuan
authors.initials: BC
authors.lastname: Chen
authors.forename: Shung-Te
authors.initials: ST
authors.lastname: Kao
authors.forename: Ching-Ju
authors.initials: CJ
authors.lastname: Liu
authors.affiliation: School of Post-Baccalaureate Chinese Medicine, Tzu Chi University, Hualien, Taiwan. yehcc0530@gmail.com.
authors.forename: Chia-Chou
authors.initials: CC
authors.lastname: Yeh
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000378:metabolism; D019833:Genistein / Q000494:pharmacology / Q000627:therapeutic use*; D056945:Hep G2 Cells; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D016328:NF-kappa B / Q000378:metabolism; D009361:Neoplasm Invasiveness; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D015398:Signal Transduction / Q000187:drug effects; D013025:Glycine max / Q000737:chemistry*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D018808:Transcription Factor AP-1 / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D016328:NF-kappa B; D010936:Plant Extracts; D018808:Transcription Factor AP-1; D019833:Genistein; D019869:Phosphatidylinositol 3-Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020780:Matrix Metalloproteinase 9; D013755:Tetradecanoylphorbol Acetate