title: The anti-metastatic efficacy of β-ionone and the possible mechanisms of action in human hepatocarcinoma SK-Hep-1 cells.
abstract: β-Ionone (BI), a precursor for carotenoids, is widely distributed in fruit and vegetables. Recent in vitro studies have demonstrated the potential anti-metastatic effects of BI, but the mechanisms underlying such actions are not clear. Because liver cancer is the most endemic cancer in Taiwan and in a large region of the world, we hereby investigate the anti-metastatic effects of BI and its mechanisms of actions in a highly metastatic human hepatocarcinoma SK-Hep-1 cells. We show that incubation of cells with BI (1-50 μm) for 24 and 48 h significantly inhibited cell invasion, migration and adhesion. Mechanistically, incubation of cells with BI (1-50 μm) for 24 h resulted in the following: (1) significant inhibition of matrix metalloproteinase (MMP)-2, MMP-9 and urokinase-type plasminogen activator activities, (2) up-regulation of protein expression of the tissue inhibitor of matrix metalloproteinase (TIMP)-1, TIMP-2 and plasminogen activator inhibitor-1, (3) down-regulation of the expression of migration-related proteins, including focal adhesion kinase (FAK), phosphorylated form of FAK, Rho, Rac1 and Cdc42 and (4) up-regulation of the expression of nm23-H1 protein (P < 0·05). Overall, the results show that BI effectively inhibits the metastasis of SK-Hep-1 cells, and this effect involves the regulation of gene expression and signal pathways related to invasion and migration.
authors.affiliation: Department of Health and Nutrition Biotechnology, Asia University, Taichung 41354, Taiwan, ROC. cshuang@asia.edu.tw
authors.forename: Chin-Shiu
authors.initials: CS
authors.lastname: Huang
authors.forename: Shih-Chieh
authors.initials: SC
authors.lastname: Lyu
authors.forename: Jen-Yin
authors.initials: JY
authors.lastname: Chen
authors.forename: Miao-Lin
authors.initials: ML
authors.lastname: Hu
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000378:metabolism* / Q000556:secondary; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement; D015536:Down-Regulation / Q000187:drug effects; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D018093:Gelatinases / Q000378:metabolism; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D054778:NM23 Nucleoside Diphosphate Kinases / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism; D045792:Norisoprenoids / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D054778:NM23 Nucleoside Diphosphate Kinases; D009363:Neoplasm Proteins; D045792:Norisoprenoids; D017395:Plasminogen Activator Inhibitor 1; C051321:SERPINE1 protein, human; D019714:Tissue Inhibitor of Metalloproteinases; C008157:beta-ionone; D051416:Focal Adhesion Protein-Tyrosine Kinases; C517938:NME1 protein, human; D014568:Urokinase-Type Plasminogen Activator; D018093:Gelatinases