Ginkgolic Acid Inhibits Invasion and Migration and TGF-ß-Induced EMT of Lung Cancer Cells Through PI3K/Akt/mTOR Inactivation.
J Cell Physiol
; 232(2): 346-354, 2017 Feb.
Article
in En
| MEDLINE
| ID: mdl-27177359
ABSTRACT
Epithelial-to-mesenchymal transition (EMT) is a critical cellular phenomenon regulating tumor metastases. In the present study, we investigated whether ginkgolic acid can affect EMT in lung cancer cells and the related underlying mechanism(s) of its actions. We found that ginkgolic acid C151 (GA C151) inhibited cell proliferation, invasion, and migration in both A549 and H1299 lung cancer cells. GA C151 also suppressed the expression of EMT related genes (Fibronectin, Vimentin, N-cadherin, MMP-9, MMP-2, Twist and Snail) and suppressed TGF-ß-induced EMT as assessed by reduced expression of mesenchymal markers (Fibronectin, Vimentin, N-cadherin), MMP-9, MMP-2, Twist and Snail. However, GA C151 did not affect the expression of various epithelial marker proteins (Occludin and E-cadherin) in both A549 and H1299 cells. TGF-ß-induced morphologic changes from epithelial to mesenchymal cells and induction of invasion and migration were reversed by GA C151. Finally, GA C151 not only abrogated basal PI3K/Akt/mTOR signaling cascade, but also reduced TGF-ß-induced phosphorylation of PI3K/Akt/mTOR pathway in lung cancer cells. Overall, these findings suggest that GA C151 suppresses lung cancer invasion and migration through the inhibition of PI3K/Akt/mTOR signaling pathway and provide a source of potential therapeutic compounds to control the metastatic dissemination of tumor cells. J. Cell. Physiol. 232 346-354, 2017. © 2016 Wiley Periodicals, Inc.
Full text:
1
Database:
MEDLINE
Main subject:
Cell Movement
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Salicylates
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Transforming Growth Factor beta
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Phosphatidylinositol 3-Kinases
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Proto-Oncogene Proteins c-akt
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Epithelial-Mesenchymal Transition
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Lung Neoplasms
Limits:
Humans
Language:
En
Journal:
J Cell Physiol
Year:
2017
Type:
Article