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Osthole inhibited TGF β-induced epithelial-mesenchymal transition (EMT) by suppressing NF-κB mediated Snail activation in lung cancer A549 cells
- Source :
- Cell adhesionmigration. 11(5-6)
- Publication Year :
- 2017
-
Abstract
- Epithelial-mesenchymal transition (EMT), the transdifferentiation of epithelial cells into mesenchymal cells, has been implicated in the metastasis and provides novel strategies for cancer therapy. Osthole (OST), a dominant active constituent of Chinese herb Cnidium monnieri, has been reported to inhibit cancer metastasis while the mechanisms remains unclear. Here, we studied the inhibitory effect and mechanisms of OST on TGF-β1-induced EMT in A549 cells. Cells were treated with TGF-β1 in the absence and presence of OST. The morphological alterations were observed with a microscopy. The protein and mRNA expressions were determined by Western blotting and real-time PCR. The protein localization was detected with immunofluorescence. The adhesion, migration, and invasion were determined by Matrigel, wound-healing, and Transwell assays. TGF-β1 treatment induced spindle-shaped alterations of cells, upregulation of N-cadherin, Vimentin, NF-κB p65, and downregulation of E-cadherin. Dysregulated membrane expression and mRNA expression of E-cadherin and N-cadherin were observed after TGF-β1 treatment. TGF-β1 increased abilities of migration and invasion and triggered the nuclear translocation of NF-κB p65. These alterations were dramatically inhibited by OST. Furthermore, PDTC, a NF-κB inhibitor, showed similar effects. In addition, TGF-β1-induced expression of Snail was significantly inhibited by OST and silenced Snail partially reversed TGF-β1-induced EMT biomarkers without affecting NF-κB p-65. In conclusion, OST inhibited TGF-β1-induced EMT, adhesion, migration, and invasion through inactivation of NF-κB-Snail pathways in A549 cells. This study provides novel molecular mechanisms for the anti-metastatic effect of OST.
- Subjects :
- 0301 basic medicine
Epithelial-Mesenchymal Transition
Lung Neoplasms
Proline
Vimentin
Biology
03 medical and health sciences
Cellular and Molecular Neuroscience
chemistry.chemical_compound
0302 clinical medicine
Downregulation and upregulation
Coumarins
Thiocarbamates
Transforming Growth Factor beta
Humans
Epithelial–mesenchymal transition
A549 cell
Matrigel
Transdifferentiation
fungi
NF-kappa B
Transcription Factor RelA
NF-κB
Cell Biology
Cadherins
Blot
030104 developmental biology
chemistry
A549 Cells
030220 oncology & carcinogenesis
Immunology
Cancer research
biology.protein
Snail Family Transcription Factors
Research Paper
Subjects
Details
- ISSN :
- 19336926
- Volume :
- 11
- Issue :
- 5-6
- Database :
- OpenAIRE
- Journal :
- Cell adhesionmigration
- Accession number :
- edsair.doi.dedup.....0edca6b359ce3c8761fcb0707a0ade4d