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Nagilactone E suppresses TGF-β1-induced epithelial-mesenchymal transition, migration and invasion in non-small cell lung cancer cells
- Source :
- Phytomedicine : international journal of phytotherapy and phytopharmacology. 52
- Publication Year :
- 2018
-
Abstract
- Background Non-small cell lung cancer (NSCLC) is one of the leading causes of cancer-related death around the world. Epithelial–mesenchymal transition (EMT) has been documented to increase motility and invasiveness of cancer cells, which promotes cancer metastasis. Purpose This study aims to investigate the inhibitory effects and mechanisms of the dinorditerpenoids and norditerpenoids isolated from the seeds of Podocarpus nagi against transforming growth factor (TGF)-β1-induced EMT. Methods A series of dinorditerpenoids and norditerpenoids were isolated from the seeds of P. nagi. Western blot and quantitative real-time PCR assays were performed to determine the expression levels of relative proteins and mRNA, along with immunofluorescence, Smad-binding element (SBE)-luciferase and chromatin immunoprecipitation (ChIP) assays for the mechanism study. Transwell assays were conducted to determine the effect of the compounds on cell migration and invasion. Results Nagilactone E (NLE) showed the superior inhibitory effect against TGF-β1-induced EMT. NLE treatment dramatically inhibited TGF-β1-induced expression of EMT markers in A549 cells. Mechanism study indicated that NLE markedly suppressed TGF-β1-induced Smad2 and Smad3 activation and nuclear translocation. SBE-luciferase and ChIP assays showed that NLE inhibited the combining of Smad3 to SBE in the promoters of the cell signaling factors. NLE co-treatment attenuated TGF-β1-induced up-regulation of the protein and mRNA levels of TGF-β receptor TβRI. Furthermore, NLE inhibited TGF-β1-stimulated cell migration and invasion, as well as up-regulation of the key signaling proteins related with migration and invasion. Conclusion NLE inhibited TGF-β/Smad signaling pathway, thereafter suppressed TGF-β1-induced EMT, migration and invasion in NSCLC A549 cells.
- Subjects :
- Cell signaling
Epithelial-Mesenchymal Transition
Lung Neoplasms
Pharmaceutical Science
SMAD
Smad2 Protein
Transforming Growth Factor beta1
03 medical and health sciences
0302 clinical medicine
Cell Movement
Carcinoma, Non-Small-Cell Lung
Drug Discovery
Humans
Neoplasm Invasiveness
Epithelial–mesenchymal transition
Smad3 Protein
030304 developmental biology
Pharmacology
A549 cell
0303 health sciences
Chemistry
Cell migration
Complementary and alternative medicine
A549 Cells
030220 oncology & carcinogenesis
Cancer cell
Seeds
Cancer research
Ferns
Molecular Medicine
Signal transduction
Diterpenes
Transforming growth factor
Signal Transduction
Subjects
Details
- ISSN :
- 1618095X
- Volume :
- 52
- Database :
- OpenAIRE
- Journal :
- Phytomedicine : international journal of phytotherapy and phytopharmacology
- Accession number :
- edsair.doi.dedup.....34620c60e5084e116cf89095c37cfe6e