Saponins from the Roots of Platycodon grandiflorum Suppresses TGF beta 1-Induced Epithelial-Mesenchymal Transition Via Repression of PI3K/Akt, ERK1/2 and Smad2/3 Pathway in Human Lung Carcinoma A549 Cells

Title
Saponins from the Roots of Platycodon grandiflorum Suppresses TGF beta 1-Induced Epithelial-Mesenchymal Transition Via Repression of PI3K/Akt, ERK1/2 and Smad2/3 Pathway in Human Lung Carcinoma A549 Cells
Author(s)
정태천최재호[최재호]황용필[황용필]김형균[김형균]Khanal T[Khanal T]Do MT[Do MT]진순우[진순우]한화정[한화정]이현선[이현선]이영춘[이영춘]정영철[정영철]정혜광[정혜광]
Keywords
TGF-BETA RECEPTOR; TETRACHLORIDE-INDUCED HEPATOTOXICITY; BREAST-CANCER CELLS; NF-KAPPA-B; GROWTH-FACTORS; IN-VITRO; METASTASIS; KINASE; ACTIVATION; INHIBITION
Issue Date
201401
Publisher
ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD
Citation
NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL, v.66, no.1, pp.140 - 151
Abstract
Transforming growth factor (TGF) is a multifunctional cytokine that induces growth arrest, tissue fibrosis, and epithelial-mesenchymal transition (EMT) through activation of Smad and non-Smad signaling pathways. EMT is the differentiation switch by which polarized epithelial cells differentiate into contractile and motile mesenchymal cells. Our previous studies have shown that saponins from the roots of Platycodon grandiflorum (CKS) have antiinflammatory, antioxidant, antimetastatic, and hepatoprotective effects. In this study, we investigated the inhibitory effect of CKS on TGF1-induced alterations characteristic of EMT in human lung carcinoma A549 cells. We found that CKS-treated cells displayed inhibited TGF1-mediated E-cadherin downregulation and Vimentin upregulation and also retained epithelial morphology. Furthermore, TGF1-increased Snail expression, a repressor of E-cadherin and an inducer of the EMT, was reduced by CKS. CKS inhibited TGF1-induced phosphorylation of Akt, ERK1/2, and glycogen synthase kinase-3 (GSK-3). Inhibition of PI3K/Akt and ERK1/2 also blocked TGF1-induced GSK-3 phosphorylation and Snail activation. Furthermore, TGF1-increased Snail expression was reduced by selective inhibitors of Akt and ERK1/2. Moreover, CKS treatment attenuated TGF1-induced Smad2/3 phosphorylation and upregulated Smad7 expression. These results indicate that pretreatment with the CKS inhibits the TGF1-induced EMT through PI3K/Akt, ERK1/2, GSK-3 and Smad2/3 in human lung carcinoma cells.
URI
http://hdl.handle.net/YU.REPOSITORY/33477http://dx.doi.org/10.1080/01635581.2014.853087
ISSN
0163-5581
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약학대학 > 약학부 > Articles
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