Acacetin, a flavonoid, inhibits the invasion and migration of human prostate cancer DU145 cells via inactivation of the p38 MAPK signaling pathway

  • Kun-Hung Shen
  • Shun-Hsing Hung
  • Li-Te Yin
  • Chun-Shui Huang
  • Chang-Hung Chao
  • Chein-Liang Liu
  • Yuan-Wei Shih
Article

Abstract

Acacetin (5,7-dihydroxy-4′-methoxyflavone), a flavonoid compound, has anti-peroxidative and anti-inflammatory effects. The effect of acacetin on antimetastasis in human prostate cancer DU-145 cells was investigated. First, the result demonstrated acacetin could exhibit an inhibitory effect on the abilities of the adhesion, invasion, and migration by cell–matrix adhesion assay, wound-healing assay, and Boyden chamber assay. Data also showed acacetin could inhibit the phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK) involved in the downregulation of the expressions of matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), and urokinase-type plasminogen activator (u-PA) at both the protein and mRNA levels. Next, acacetin significantly decreased the nuclear levels of nuclear factor kappa B (NF-κB), c-Fos, and c-Jun. Also, the treatment with acacetin to DU145 cells also leads to a dose-dependent inhibition on the binding ability of NF-κB and activator protein-1 (AP-1). Furthermore, the treatment of inhibitors specific for p38 MAPK (SB203580) to DU145 cells could cause reduced expressions of MMP-2, MMP-9, and u-PA. These results showed acacetin could inhibit the invasion and migration abilities of DU145 cells by reducing MMP-2, MMP-9, and u-PA expressions through suppressing p38 MAPK signaling pathway and inhibiting NF-κB- or AP-1-binding activity. These findings proved acacetin might be offered further application as an antimetastatic agent.

Keywords

Acacetin Invasion Migration p38 MAPK MMP-2 MMP-9 u-PA 

Abbreviations

MMPs

Matrix metalloproteinases

u-PA

Urokinase-type plasminogen activator

ECM

Extracellular matrix

ERK

Extracellular signal-regulated kinase

JNK/SAPK

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

p38 MAPK

p38 Mitogen-activated protein kinase

PI3K

Phosphoinositide 3-kinase

NF-κB

Nuclear factor kappa B

AP-1

Activator protein-1

IκB

Inhibitor of NF-κB

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Copyright information

© Springer Science+Business Media, LLC. 2009

Authors and Affiliations

  • Kun-Hung Shen
    • 1
    • 2
    • 3
  • Shun-Hsing Hung
    • 1
  • Li-Te Yin
    • 4
  • Chun-Shui Huang
    • 5
  • Chang-Hung Chao
    • 6
  • Chein-Liang Liu
    • 1
  • Yuan-Wei Shih
    • 4
  1. 1.Division of Urology, Department of SurgeryChi Mei Medical CenterTainanTaiwan
  2. 2.Department of Childhood Education and NurseryChia Nan University of Pharmacy and ScienceTainanTaiwan
  3. 3.Department of UrologyTaipei Medical UniversityTaipeiTaiwan
  4. 4.Department of Biological Science and Technology, Graduate Institute of Biomedical ScienceChung Hwa University of Medical TechnologyTainanTaiwan
  5. 5.Department of Medical TechnologyKuo General HospitalTainanTaiwan
  6. 6.Department of NeurologyKuo General HospitalTainanTaiwan

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