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Nagilactone E suppresses TGF-β1-induced epithelial–mesenchymal transition, migration and invasion in non-small cell lung cancer cells
Zhang L.-L.2; Jiang X.-M.2; Huang M.-Y.2; Feng Z.-L.2; Chen X.2; Wang Y.2; Li H.1; Li A.3; Lin L.-G.2; Lu J.-J.2
2019
Source PublicationPhytomedicine
ISSN1618095X 09447113
Volume52Pages:32-39
AbstractBackground: 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.
KeywordEpithelial-mesenchymal transition Nagilactone E Smad TGF-β1
DOI10.1016/j.phymed.2018.09.222
URLView the original
Language英語
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Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Affiliation1.Huazhong University of Science and Technology
2.Universidade de Macau
3.Chongqing University of Technology
Recommended Citation
GB/T 7714
Zhang L.-L.,Jiang X.-M.,Huang M.-Y.,et al. Nagilactone E suppresses TGF-β1-induced epithelial–mesenchymal transition, migration and invasion in non-small cell lung cancer cells[J]. Phytomedicine,2019,52:32-39.
APA Zhang L.-L..,Jiang X.-M..,Huang M.-Y..,Feng Z.-L..,Chen X..,...&Lu J.-J..(2019).Nagilactone E suppresses TGF-β1-induced epithelial–mesenchymal transition, migration and invasion in non-small cell lung cancer cells.Phytomedicine,52,32-39.
MLA Zhang L.-L.,et al."Nagilactone E suppresses TGF-β1-induced epithelial–mesenchymal transition, migration and invasion in non-small cell lung cancer cells".Phytomedicine 52(2019):32-39.
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