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   <subfield code="a">α-Mangostin Suppresses Phorbol 12-myristate 13-acetate-Induced MMP-2/MMP-9 Expressions via αvβ3 Integrin/FAK/ERK and NF-κB Signaling Pathway in Human Lung Adenocarcinoma A549 Cells</subfield>
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   <subfield code="c">[Yuan-Wei Shih, Shang-Tao Chien, Pin-Shern Chen, Jian-Hui Lee, Shu-Hau Wu, Li-Te Yin]</subfield>
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   <subfield code="a">The purpose of this study is to investigate the anti-metastatic effect of α-mangostin on phorbol 12-myristate 13-acetate (PMA)-induced matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) expressions in A549 human lung adenocarcinoma cells. Firstly, α-mangostin could inhibit PMA-induced abilities of the adhesion, invasion, and migration. Data also showed α-mangostin could inhibit the activation of αvβ3 integrin, focal adhesion kinase (FAK), and extracellular signal-regulated kinase1/2 (ERK1/2) involved in the downregulation the enzyme activities, protein and messenger RNA levels of MMP-2 and MMP-9 induced by PMA. Next, α-mangostin also strongly inhibited PMA-induced degradation of inhibitor of kappaBα (IκBα) and the nuclear levels of nuclear factor kappa B (NF-κB). Also, a dose-dependent inhibition on the binding abilities of NF-κB by α-mangostin treatment was further observed. Furthermore, reduction of FAK or ERK1/2 phosphorylation by FAK small interfering RNA (FAK siRNA) potentiated the effect of α-mangostin. Finally, the transient transfection of ERK siRNA significantly down-regulated the expressions of MMP-2 and MMP-9 concomitantly with a marked inhibition on cell invasion and migration. Presented results indicated α-mangostin is a novel, effect, anti-metastatic agent that functions by downregulating MMP-2 and MMP-9 gene expressions.</subfield>
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   <subfield code="a">Springer Science+Business Media, LLC, 2010</subfield>
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   <subfield code="a">α-Mangostin</subfield>
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   <subfield code="a">PMA</subfield>
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   <subfield code="a">Invasion</subfield>
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   <subfield code="a">Migration</subfield>
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   <subfield code="a">αvβ3 Integrin</subfield>
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   <subfield code="a">FAK</subfield>
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   <subfield code="a">ERK1/2</subfield>
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   <subfield code="a">MMP-2</subfield>
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   <subfield code="a">MMP-9</subfield>
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   <subfield code="a">PMA : Phorbol 12-myristate 13-acetate</subfield>
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   <subfield code="a">MMPs : Matrix metalloproteinases</subfield>
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   <subfield code="a">ECM : Extracellular matrix</subfield>
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   <subfield code="a">ERK : Extracellular signaling-regulating kinase</subfield>
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   <subfield code="a">JNK/SAPK : c-Jun N-terminal kinase/stress-activated protein kinase</subfield>
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   <subfield code="a">p38 MAPK : p38 Mitogen-activated protein kinase</subfield>
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   <subfield code="a">PI3K/Akt : Phosphoinositide 3-kinase/protein kinase B</subfield>
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   <subfield code="a">NF-κB : Nuclear factor kappa B</subfield>
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   <subfield code="a">IκBα : Inhibitor of NF-κB</subfield>
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   <subfield code="a">Shih</subfield>
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   <subfield code="u">Department of Biological Science and Technology and Graduate Institute of Biomedical Science, Chung Hwa University of Medical Technology, No. 89, Wen-Hwa 1st Street, Jen-Te, 717, Tainan, Taiwan</subfield>
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   <subfield code="a">Chien</subfield>
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   <subfield code="t">Cell Biochemistry and Biophysics</subfield>
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