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Nagilactone E suppresses TGF-beta 1-induced epithelial-mesenchymal transition, migration and invasion in non-small cell lung cancer cells
Le-Le Zhang1; Xiao-Ming Jiang1; Mu-Yang Huang1; Zhe-Ling Feng1; Xiuping Chen1; Yitao Wang1; Hua Li2; Ao Li3; Li-Gen Lin1; Jin-Jian Lu1
2019-01
Source PublicationPHYTOMEDICINE
ISSN0944-7113
Volume52Pages:32-39
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 blotand 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 im-munoprecipitation (ChIP) assays for the mechanism study. Transwell assays were conducted to determine theeffect 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 ofTGF-βreceptor TβRI. Furthermore, NLE inhibited TGF-β1-stimulated cell migration and invasion, as well as upregulation of the key signaling proteins related with migration and invasion.

Conclusion:NLE inhibited TGF-β/Smad signaling pathway, thereafter suppressed TGF-β1-induced EMT, mi-gration and invasion in NSCLC A549 cells.

KeywordNagilactone e Tgf-β1 Epithelial-mesenchymal Transitio Smad
DOI10.1016/j.phymed.2018.09.222
Indexed BySCI
Language英语
WOS Research AreaPlant Sciences ; Pharmacology & Pharmacy ; Integrative & Complementary Medicine
WOS SubjectPlant Sciences ; Chemistry, Medicinal ; Integrative & Complementary Medicine ; Pharmacology & Pharmacy
WOS IDWOS:000459934000004
PublisherELSEVIER GMBH, HACKERBRUCKE 6, 80335 MUNICH, GERMANY
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Document TypeJournal article
专题Institute of Chinese Medical Sciences
Corresponding AuthorLi-Gen Lin; Jin-Jian Lu
Affiliation1.State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China
2.Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science andTechnology, Wuhan, China
3.College of Pharmacy and Bioengineering, Chongqing University of Technology, Chongqing, China
First Author AffilicationInstitute of Chinese Medical Sciences
Corresponding Author AffilicationInstitute of Chinese Medical Sciences
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Le-Le Zhang,Xiao-Ming Jiang,Mu-Yang Huang,et al. Nagilactone E suppresses TGF-beta 1-induced epithelial-mesenchymal transition, migration and invasion in non-small cell lung cancer cells[J]. PHYTOMEDICINE,2019,52:32-39.
APA Le-Le Zhang.,Xiao-Ming Jiang.,Mu-Yang Huang.,Zhe-Ling Feng.,Xiuping Chen.,...&Jin-Jian Lu.(2019).Nagilactone E suppresses TGF-beta 1-induced epithelial-mesenchymal transition, migration and invasion in non-small cell lung cancer cells.PHYTOMEDICINE,52,32-39.
MLA Le-Le Zhang,et al."Nagilactone E suppresses TGF-beta 1-induced epithelial-mesenchymal transition, migration and invasion in non-small cell lung cancer cells".PHYTOMEDICINE 52(2019):32-39.
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