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Molecular and Cellular Biochemistry

, Volume 335, Issue 1–2, pp 181–193 | Cite as

Plumbagin inhibits TPA-induced MMP-2 and u-PA expressions by reducing binding activities of NF-κB and AP-1 via ERK signaling pathway in A549 human lung cancer cells

  • Jiunn-Min Shieh
  • Tai-An Chiang
  • Wen-Teng Chang
  • Chang-Hung Chao
  • Yi-Chieh Lee
  • Guan-Yu Huang
  • You-Xin Shih
  • Yuan-Wei Shih
Article

Abstract

This study first investigates the anti-metastatic effect of plumbagin (5-hydroxy-2-methyl-1,4-naphthoquinone) on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced MMPs and u-PA expressions in human lung cancer cells, A549. First, the result demonstrated plumbagin could inhibit TPA induced the abilities of the adhesion, invasion, and migration by cell–matrix adhesion assay and Boyden chamber assay. Data also showed plumbagin could inhibit the activation of extracellular signal-regulated kinase 1 and 2 (ERK1/2) involved in the down-regulating enzyme activities, protein and messenger RNA levels of matrix metalloproteinase-2 (MMP-2), and urokinase-type plasminogen activator (u-PA) induced by TPA. Next, plumbagin also strongly inhibited TPA-induced phosphorylation and degradation of inhibitor of kappaBα (IκBα), and the nuclear levels of nuclear factor kappa B (NF-κB), c-Fos, and c-Jun. Also, a dose-dependent inhibition on the binding abilities of NF-κB and activator protein-1 (AP-1) by plumbagin treatment was further observed. Further, the treatment of specific inhibitor for ERK (U0126) to A549 cells could inhibit TPA-induced MMP-2 and u-PA expressions along with an inhibition on cell invasion and migration. Presented data reveals that plumbagin is a novel, effective, anti-metastatic agent that functions by down-regulating MMP-2 and u-PA gene expressions.

Keywords

Plumbagin Invasion Migration ERK1/2 MMP-2 u-PA 

Abbreviations

TPA

12-O-tetradecanoylphorbol-13-acetate

MMPs

Matrix metalloproteinases

u-PA

Urokinase-type plasminogen activator

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

AP-1

Activator protein-1

IκB

Inhibitor of NF-κB

IκK

IκB kinase

Notes

Acknowledgment

This work was supported by the grant from the Subsidized Project of the Chung Hwa University, Tainan, Taiwan (97-HT-08011).

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Copyright information

© Springer Science+Business Media, LLC. 2009

Authors and Affiliations

  • Jiunn-Min Shieh
    • 1
  • Tai-An Chiang
    • 2
  • Wen-Teng Chang
    • 3
  • Chang-Hung Chao
    • 4
  • Yi-Chieh Lee
    • 3
  • Guan-Yu Huang
    • 3
  • You-Xin Shih
    • 5
  • Yuan-Wei Shih
    • 3
  1. 1.Department of Pulmonary MedicineChi Mei Medical CenterTainanTaiwan
  2. 2.Department of Medical Technology and Institute of Biological Science and TechnologyChung Hwa University of Medical TechnologyTainanTaiwan
  3. 3.Department of Biological Science and Technology and Institute of Biomedical ScienceChung Hwa University of Medical TechnologyTainanTaiwan
  4. 4.Department of NeurologyKuo General HospitalTainanTaiwan
  5. 5.Taipei Municipal Song Shan Senior High SchoolTaipeiTaiwan

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