Anethole Exerts Antimetatstaic Activity via Inhibition of Matrix Metalloproteinase 2/9 and AKT/Mitogen-Activated Kinase/Nuclear Factor Kappa B Signaling Pathways
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概要
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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.
著者
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KIM Sung-Hoon
College of Oriental Medicine, Kyunghee University
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Jung Ji
College Of Pharmacy Sungkyunkwan University
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Jeong Soo-Jin
College of Oriental Medicine, Kyung Hee University
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Lee Hyo-Jung
College of Oriental Medicine, Kyung Hee University
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Lee Hyo-Jeong
College of Oriental Medicine, Kyung Hee University
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KIM Dae
College of Veterinary Medicine and Research Institute of Veterinary Medicine, Chungbuk National Univ
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Jung Ji
College Of Pharmacy Catholic University Of Daegu
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Choo Eun
College of Oriental Medicine, Kyung Hee University
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Rhee Yun-Hee
College of Oriental Medicine, Kyung Hee University
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Kim Hyun
Yonsei University School of Medicine
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Ko Hyun
College of Oriental Medicine, Kyung Hee University
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Kim Ji-Hyun
College of Oriental Medicine, Kyung Hee University
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Kwon Tae-Rin
College of Oriental Medicine, Kyung Hee University
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Kim Jin
College of Oriental Medicine, Kyung Hee University
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Lee Eun-Ok
College of Oriental Medicine, Kyung Hee University
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Chen Chang-Yan
Beth Israel Deaconess Medical Center, Harvard Medical School
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Kim Dae
College Of Pharmacy Seoul National University
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Kim Dae
College Of Pharmacy Chung-ang University
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Kim Dae
College Of Life Sciences And Biotechnology Korea University
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Kim Sung-Hoon
College of Oriental Medicine, Kyung Hee University
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Kim Dae
College of Pharmacy, Woosuk University
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Jung Ji
College of Oriental Medicine, Kyung Hee University
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