title: Anethole exerts antimetatstaic activity via inhibition of matrix metalloproteinase 2/9 and AKT/mitogen-activated kinase/nuclear factor kappa B signaling pathways.
abstract: Anethole is known to possess anti-inflammatory and anti-tumor activities and to be a main constituent of fennel, anise, and camphor. In the present study, we evaluated anti-metastatic and apoptotic effects of anethole on highly-metastatic HT-1080 human fibrosarcoma tumor cells. Despite weak cytotoxicity against HT-1080 cells, anethole inhibited the adhesion to Matrigel and invasion of HT-1080 cells in a dose-dependent manner. Anethole was also able to down-regulate the expression of matrix metalloproteinase (MMP)-2 and -9 and up-regulate the gene expression of tissue inhibitor of metalloproteinase (TIMP)-1. The similar inhibitory effect of anethole on MMP-2 and -9 activities was confirmed by zymography assay. Furthermore, anethole significantly decreased mRNA expression of urokinase plasminogen activator (uPA), but not uPA receptor (uPAR). In addition, anethole suppressed the phosphorylation of AKT, extracellular signal-regulated kinase (ERK), p38 and nuclear transcription factor kappa B (NF-κB) in HT-1080 cells. Taken together, our findings indicate that anethole is a potent anti-metastatic drug that functions through inhibiting MMP-2/9 and AKT/mitogen-activated protein kinase (MAPK)/NF-κB signal transducers.
authors.affiliation: College of Oriental Medicine, Kyung Hee University, Seoul 130–701, South Korea.
authors.forename: Eun Jeong
authors.initials: EJ
authors.lastname: Choo
authors.forename: Yun-Hee
authors.initials: YH
authors.lastname: Rhee
authors.forename: Soo-Jin
authors.initials: SJ
authors.lastname: Jeong
authors.forename: Hyo-Jung
authors.initials: HJ
authors.lastname: Lee
authors.forename: Hyun Seok
authors.initials: HS
authors.lastname: Kim
authors.forename: Hyun Suk
authors.initials: HS
authors.lastname: Ko
authors.forename: Ji-Hyun
authors.initials: JH
authors.lastname: Kim
authors.forename: Tae-Rin
authors.initials: TR
authors.lastname: Kwon
authors.forename: Ji Hoon
authors.initials: JH
authors.lastname: Jung
authors.forename: Jin Hyoung
authors.initials: JH
authors.lastname: Kim
authors.forename: Hyo-Jeong
authors.initials: HJ
authors.lastname: Lee
authors.forename: Eun-Ok
authors.initials: EO
authors.lastname: Lee
authors.forename: Dae Keun
authors.initials: DK
authors.lastname: Kim
authors.forename: Chang-Yan
authors.initials: CY
authors.lastname: Chen
authors.forename: Sung-Hoon
authors.initials: SH
authors.lastname: Kim
mesh_terms: D000081248:Allylbenzene Derivatives; D000818:Animals; D000840:Anisoles / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D006801:Humans; D061965:Matrix Metalloproteinase Inhibitors; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors*; D015394:Molecular Structure; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D009362:Neoplasm Metastasis / Q000517:prevention & control; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors*; D015398:Signal Transduction
chemical_list: D000081248:Allylbenzene Derivatives; D000840:Anisoles; D061965:Matrix Metalloproteinase Inhibitors; D016328:NF-kappa B; D051057:Proto-Oncogene Proteins c-akt; D020929:Mitogen-Activated Protein Kinase Kinases; C006578:anethole