Anethole Exerts Antimetatstaic Activity via Inhibition of Matrix Metalloproteinase 2/9 and AKT/Mitogen-Activated Kinase/Nuclear Factor Kappa B Signaling Pathways

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 cytotoxi...

Full description

Saved in:
Bibliographic Details
Published in:Biological & Pharmaceutical Bulletin 2011/01/01, Vol.34(1), pp.41-46
Main Authors: Choo, Eun Jeong, Rhee, Yun-Hee, Jeong, Soo-Jin, Lee, Hyo-Jung, Kim, Hyun Seok, Ko, Hyun Suk, Kim, Ji-Hyun, Kwon, Tae-Rin, Jung, Ji Hoon, Kim, Jin Hyoung, Lee, Hyo-Jeong, Lee, Eun-Ok, Kim, Dae Keun, Chen, Chang-Yan, Kim, Sung-Hoon
Format: Article
Language:English
Subjects:
AKT
anethole
Animals
Anisoles - chemistry
Anisoles - pharmacology
antimetastasis
Cell Line, Tumor
Dose-Response Relationship, Drug
Humans
matrix metalloproteinase
Matrix Metalloproteinase Inhibitors
mitogen-activated kinase
Mitogen-Activated Protein Kinase Kinases - antagonists & inhibitors
Molecular Structure
Neoplasm Metastasis - prevention & control
NF-kappa B - antagonists & inhibitors
nuclear transcription factor kappa B
Proto-Oncogene Proteins c-akt - antagonists & inhibitors
Signal Transduction
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0918-6158
1347-5215
DOI:10.1248/bpb.34.41