Osthole inhibits the invasive ability of human lung adenocarcinoma cells via suppression of NF-κB-mediated matrix metalloproteinase-9 expression

Shang Jyh Kao, Jen Liang Su, Chi Kuan Chen, Ming Chih Yu, Kuan Jen Bai, Jer Hua Chang, Mauo Ying Bien, Shun Fa Yang, Ming Hsien Chien

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

The induction of matrix metalloproteinase (MMP)-9 is particularly important for the invasiveness of various cancer cells. Osthole, a natural coumarin derivative extracted from traditional Chinese medicines, is known to inhibit the proliferation of a variety of tumor cells, but the effect of osthole on the invasiveness of tumor cells is largely unknown. This study determines whether and by what mechanism osthole inhibits invasion in CL1-5 human lung adenocarcinoma cells. Herein, we found that osthole effectively inhibited the migratory and invasive abilities of CL1-5 cells. A zymographic assay showed that osthole inhibited the proteolytic activity of MMP-9 in CL1-5 cells. Inhibition of migration, invasion, and MMP2 and/or MMP-9 proteolytic activities was also observed in other lung adenocarcinoma cell lines (H1299 and A549). We further found that osthole inhibited MMP-9 expression at the messenger RNA and protein levels. Moreover, a chromatin immunoprecipitation assay showed that osthole inhibited the transcriptional activity of MMP-9 by suppressing the DNA binding activity of nuclear factor (NF)-κB in the MMP-9 promoter. Using reporter assays with point-mutated promoter constructs further confirmed that the inhibitory effect of osthole requires an NF-κB binding site on the MMP-9 promoter. Western blot and immunofluorescence assays demonstrated that osthole inhibited NF-κB activity by inhibiting IκB-α degradation and NF-κB p65 nuclear translocation. In conclusion, we demonstrated that osthole inhibits NF-κB-mediated MMP-9 expression, resulting in suppression of lung cancer cell invasion and migration, and osthole might be a potential agent for preventing the invasion and metastasis of lung cancer.

Original languageEnglish
Pages (from-to)105-115
Number of pages11
JournalToxicology and Applied Pharmacology
Volume261
Issue number1
DOIs
Publication statusPublished - May 15 2012

Fingerprint

Matrix Metalloproteinase 9
Cells
Assays
Tumors
Lung Neoplasms
osthol
Adenocarcinoma of lung
Coumarins
Neoplasms
Chromatin Immunoprecipitation
Matrix Metalloproteinase 2
Chinese Traditional Medicine
Medicine
Chromatin
Cell Movement
Fluorescent Antibody Technique
Western Blotting
Binding Sites
Neoplasm Metastasis
Degradation

Keywords

  • Invasion
  • Lung adenocarcinoma
  • Migration
  • MMPs
  • NF-κB
  • Osthole

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology

Cite this

Osthole inhibits the invasive ability of human lung adenocarcinoma cells via suppression of NF-κB-mediated matrix metalloproteinase-9 expression. / Kao, Shang Jyh; Su, Jen Liang; Chen, Chi Kuan; Yu, Ming Chih; Bai, Kuan Jen; Chang, Jer Hua; Bien, Mauo Ying; Yang, Shun Fa; Chien, Ming Hsien.

In: Toxicology and Applied Pharmacology, Vol. 261, No. 1, 15.05.2012, p. 105-115.

Research output: Contribution to journalArticle

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AU - Bai, Kuan Jen

AU - Chang, Jer Hua

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