title: Antimetastatic effects of α-carotene and possible mechanisms of action in human hepatocarcinoma SK-Hep-1 cells.
abstract: In vitro evidence suggests that α-carotene (AC) is an antimetastatic agent against cancer cells, but the mechanistic action is unclear. This study investigated the antimetastatic effect and possible mechanism of AC in comparison with β-carotene (BC) using human hepatocarcinoma SK-Hep-1 cells. Results reveal that treatment with AC (0.5-2.5 μM) for 48 h significantly inhibited invasion, migration, and adhesion of SK-Hep-1 cells in a concentration-dependent manner. These effects of AC were stronger than those of BC at the same concentration (2.5 μM). Mechanistically, AC significantly decreased activities of urokinase plasminogen activator and matrix metalloproteinases (MMP)-2 and -9, but increased protein expression of plasminogen activator inhibitor-1, tissue inhibitor of MMP (TIMP)-1 and -2, and nm23-H1, an antimetastatic protein. AC also attenuated focal adhesion kinase-mediated phosphorylation of mitogen-activated protein kinase family resulting in decreased protein expression of Rho and Rac 1. Overall, these data suggest that AC has potential as an antimetastatic agent.
authors.affiliation: Department of Food Science and Biotechnology, National Chung Hsing University , Taichung, Taiwan 402.
authors.forename: Huei-Yan
authors.initials: HY
authors.lastname: Chen
authors.forename: Te-Cheng
authors.initials: TC
authors.lastname: Yueh
authors.forename: Yi-Chuan
authors.initials: YC
authors.lastname: Chen
authors.forename: Chien-Hao
authors.initials: CH
authors.lastname: Huang
authors.forename: Chih-Min
authors.initials: CM
authors.lastname: Yang
authors.forename: Miao-Lin
authors.initials: ML
authors.lastname: Hu
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002338:Carotenoids / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy / Q000473:pathology*; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D009362:Neoplasm Metastasis; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D002338:Carotenoids; C041635:alpha-carotene; D020928:Mitogen-Activated Protein Kinases; D014568:Urokinase-Type Plasminogen Activator; D020778:Matrix Metalloproteinase 2