Ginkgolic Acid Inhibits Invasion and Migration and TGF‐β‐Induced EMT of Lung Cancer Cells Through PI3K/Akt/mTOR Inactivation

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 C15:1 (GA C15:1) inhibited cell proliferation, invasion, and migration in both A549 and H1299 lung cancer cells. GA C15:1 also suppressed the expression of EMT related genes (Fibronectin, Vimentin, N-cadherin, MMP-9, MMP-2, Twist and Snail) and suppressed TGF-β-induced EMT as assessed by reduced expression of mesenchymal markers (Fibronectin, Vimentin, N-cadherin), MMP-9, MMP-2, Twist and Snail. However, GA C15:1 did not affect the expression of various epithelial marker proteins (Occludin and E-cadherin) in both A549 and H1299 cells. TGF-β-induced morphologic changes from epithelial to mesenchymal cells and induction of invasion and migration were reversed by GA C15:1. Finally, GA C15:1 not only abrogated basal PI3K/Akt/mTOR signaling cascade, but also reduced TGF-β-induced phosphorylation of PI3K/Akt/mTOR pathway in lung cancer cells. Overall, these findings suggest that GA C15:1 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.

Ginkgolic acids inhibit migration in breast cancer cells by inhibition of NEMO sumoylation and NF-κB activity

“…Previous studies have shown that GA exhibit promising antitumor activities. The wound-healing and anti-migratory effects on pancreatic and lung cancer have been previously described [12, 14]. We found that GA have anti-migratory effects on the triple-negative MDA-MB-231 breast cancer cell line as well as in the less invasive MCF-7 cells.…”

“…The viability of pancreatic cancer cells was suppressed by GA. In addition, GA induced apoptosis and impaired migration, invasion and the colony-forming capability of cancer cells [12–14]. GA also inhibited de novo lipogenesis in cancer cells by activation of AMP-activated protein kinase (AMPK) signaling and downregulation of several key enzymes involved in this process [14].…”

“…Furthermore, GA induced apoptosis by down-regulation of BCL-2 and up-regulation of Bax [13]. They also suppressed lung cancer migration and invasion by inhibition of the PI3K/Akt/mTOR signaling pathway [12]. …”

Ginkgolic Acid Protects against Aβ-Induced Synaptic Dysfunction in the Hippocampus

“…In addition, a recent work suggested that GA inactivates PI3K/Akt/mTOR in lung cancer cells (Baek et al, 2016). The PI3K/Akt/mTOR is a crucial pathway regulating autophagy and synaptic plasticity in the brain (Heras-Sandoval et al, 2014).…”

Oridonin inhibits migration, invasion, adhesion and TGF‑β1‑induced epithelial‑mesenchymal transition of melanoma cells by inhibiting the activity of PI3K/Akt/GSK‑3β signaling pathway

“…Accordingly, we chose the classic EMT markers E-cadherin, β-catenin, vimentin and Snail for evaluation of the effect of ORI on EMT. TGF-β1 is the most well characterized factor responsible for induction of EMT (53,54). In our preliminary experiment, without the addition of TGF-β1, the EMT marker not changed obviously in A375 and B16-F10 cells, so we can not well evaluated the ORI's effect on EMT (data not shown).…”