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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

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Abstract

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.

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Abbreviations

PMA:

Phorbol 12-myristate 13-acetate

MMPs:

Matrix metalloproteinases

ECM:

Extracellular matrix

ERK:

Extracellular signaling-regulating kinase

JNK/SAPK:

c-Jun N-terminal kinase/stress-activated protein kinase

p38 MAPK:

p38 Mitogen-activated protein kinase

PI3K/Akt:

Phosphoinositide 3-kinase/protein kinase B

NF-κB:

Nuclear factor kappa B

IκBα:

Inhibitor of NF-κB

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Authors and Affiliations

  1. 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, Tainan, 717, Taiwan

    Yuan-Wei Shih, Jian-Hui Lee, Shu-Hau Wu & Li-Te Yin

  2. Department of Optometry, Chung Hwa University of Medical Technology, No. 89, Wen-Hwa 1st Street, Jen-Te, Tainan, 717, Taiwan

    Li-Te Yin

  3. Department of Pathology, Kaohsiung Armed Forces General Hospital, No. 2, Chung-Zhang, 1st Road, Kaohsiung, 802, Taiwan

    Shang-Tao Chien

  4. Department of Biological Science and Technology, Chia Nan University of Pharmacy & Science, No. 60, Section 1, Erh-Jen Road, Jen-Te, Tainan, 717, Taiwan

    Pin-Shern Chen

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  1. Yuan-Wei Shih
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Shih, YW., Chien, ST., Chen, PS. et al. 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. Cell Biochem Biophys 58, 31–44 (2010). https://doi.org/10.1007/s12013-010-9091-2

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