Resveratrol inhibits TGF-β1-induced epithelial-to-mesenchymal transition and suppresses lung cancer invasion and metastasis.

Epithelial-to-mesenchymal transition (EMT) is a cellular process during which epithelial polarized cells become motile mesenchymal-appearing cells, which in turn promotes carcinoma invasion and metastasis. Resveratrol (trans-3,4',5-trihydroxystilbene) is a natural polyphenolic compound found in grapes, red wine and several other plants. Numerous reports in the literature indicate that resveratrol can suppress cancer invasion and metastasis. However, the underlying mechanisms of inhibiting metastasis by resveratrol are complex, not fully elucidated and the subject of intense scientific debate. Despite evidence indicating that EMT can be a target for resveratrol, little is known about the effect of resveratrol on lung cancer cells. Our previous studies demonstrated that TGF-β1 induces EMT to promote lung adenocarcinoma invasion and metastasis. To understand the repressive role of resveratrol in lung cancer invasion and metastasis, we sought to investigate the potential use of resveratrol as an inhibitor of TGF-β1-induced EMT development in A549 lung cancer cells in vitro. Here we show that when A549 cells are treated with TGF-β1 and resveratrol, the latter inhibits the initiation of TGF-β1-induced EMT. Our results show that 20 μM resveratrol increases expression of the epithelial phenotype marker E-cadherin and represses the expression of the mesenchymal phenotype markers, Fibronectin and Vimentin during the initiation of TGF-β1-induced EMT. Resveratrol also inhibits expression of EMT-inducing transcription factors Snail1 and Slug, although the expression of the Twist1 transcription factor remained unchanged. Resveratrol inhibits the TGF-β1-induced increase in cell adhesion, migration and invasion of A549 lung cancer cells. Taken together, our findings provide new evidence that resveratrol suppresses lung cancer invasion and metastasis in vitro through inhibiting TGF-β1-induced EMT.

Wang H ，Zhang H ，Tang L ，Chen H ，Wu C ，Zhao M ，Yang Y ，Chen X ，Liu G ... -  《-》

Resveratrol suppresses epithelial-to-mesenchymal transition in colorectal cancer through TGF-β1/Smads signaling pathway mediated Snail/E-cadherin expression.

Ji Q ，Liu X ，Han Z ，Zhou L ，Sui H ，Yan L ，Jiang H ，Ren J ，Cai J ，Li Q ... -  《BMC CANCER》

Stereospecific effects of ginsenoside 20-Rg3 inhibits TGF-β1-induced epithelial-mesenchymal transition and suppresses lung cancer migration, invasion and anoikis resistance.

The epithelial-mesenchymal transition (EMT) is a pivotal cellular process during which epithelial polarized cells become motile mesenchymal-appearing cells, which, in turn, promotes the metastatic potential of cancer. Ginseng is a perennial plant belonging to the genus Panax that exhibits a wide range of pharmacological and physiological activities. Ginsenosides 20-Rg3, which is the active component of ginseng, has various medical effects, such as anti-tumorigenic, anti-angiogenesis, and anti-fatiguing activities. In addition, ginsenosides 20(S)-Rg3 and 20(R)-Rg3 are epimers, and this epimerization is produced by steaming. However, the possible role of 20(S)-Rg3 and 20(R)-Rg3 in the EMT is unclear. We investigated the effect of 20(S)-Rg3 and 20(R)-Rg3 on the EMT. Transforming growth factor-beta 1 (TGF-β1) induces the EMT to promote lung adenocarcinoma migration, invasion, and anoikis resistance. To understand the repressive role of 20(S)-Rg3 and 20(R)-Rg3 in lung cancer migration, invasion, and anoikis resistance, we investigated the potential use of 20(S)-Rg3 and 20(R)-Rg3 as inhibitors of TGF-β1-induced EMT development in A549 lung cancer cells in vitro. Here, we show that 20(R)-Rg3, but not 20(S)-Rg3, markedly increased expression of the epithelial marker E-cadherin and repressed Snail upregulation and expression of the mesenchymal marker vimentin during initiation of the TGF-β1-induced EMT. 20(R)-Rg3 also inhibited the TGF-β1-induced increase in cell migration, invasion, and anoikis resistance of A549 lung cancer cells. Additionally, 20(R)-Rg3 markedly inhibited TGF-β1-regulated matrix metalloproteinase-2 and activation of Smad2 and p38 mitogen activated protein kinase. Taken together, our findings provide new evidence that 20(R)-Rg3 suppresses lung cancer migration, invasion, and anoikis resistance in vitro by inhibiting the TGF-β1-induced EMT.

Kim YJ ，Choi WI ，Jeon BN ，Choi KC ，Kim K ，Kim TJ ，Ham J ，Jang HJ ，Kang KS ，Ko H ... -  《-》

Geraniin inhibits TGF-β1-induced epithelial-mesenchymal transition and suppresses A549 lung cancer migration, invasion and anoikis resistance.

The epithelial-mesenchymal transition (EMT) is an important cellular process during which epithelial polarized cells become motile mesenchymal-appeared cells, which, in turn, induces the metastatic of cancer. Geraniin is a polyphenolic component isolated from Phyllanthus amarus, which exhibits a wide range of pharmacological and physiological activities, such as antitumor, anti-hyperglycemic, anti-hypertensive, antimicrobial, and antiviral activities. However, the possible role of geraniin in the EMT is unclear. We investigated the effect of geraniin on the EMT. Transforming growth factor-beta 1 (TGF-β1) induces the EMT to promote lung adenocarcinoma migration, invasion, and anoikis resistance. To understand the suppressive role of geraniin in lung cancer migration, invasion, and anoikis resistance, we investigated the use of geraniin as inhibitors of TGF-β1-induced EMT in A549 lung cancer cells in vitro. Here, we show that geraniin remarkably increased expression of the epithelial marker E-cadherin and repressed Snail upregulation and expression of the mesenchymal marker N-cadherin and vimentin during the TGF-β1-induced EMT. Geraniin also inhibited the TGF-β1-induced increase in cell migration, invasion, and anoikis resistance of A549 lung cancer cells. Additionally, geraniin markedly inhibited TGF-β1-regulated activation of Smad2. Taken together, our findings provide new evidence that geraniin suppresses lung cancer migration, invasion, and anoikis resistance in vitro by inhibiting the TGF-β1-induced EMT.

Ko H 《-》

Sanguiin H6 suppresses TGF-β induction of the epithelial-mesenchymal transition and inhibits migration and invasion in A549 lung cancer.

In the epithelial-mesenchymal transition (EMT), an important cellular process, epithelial cells become mesenchymal cells. This process is also critically involved in cancer metastasis. Sanguiin H6 is a compound derived from ellagitannin, which is found in berries. Sanguiin H6 shows various pharmacological properties, including anti-angiogenic activity. Because the possible role of sanguiin H6 in the EMT and the underlying molecular mechanisms are unclear, we investigated the effect of sanguiin H6 on the EMT. Transforming growth factor-beta 1 (TGF-β1) induces the EMT and promotes lung adenocarcinoma migration and invasion through the Smad2/3 signaling pathway. Thus, to understand the inhibitory effects of sanguiin H6 on lung cancer migration and invasion, we investigated the ability of sanguiin H6 to inhibit TGF-β1-induced EMT in the A549 cell line. We found that sanguiin H6 significantly prevented the activation of Smad2/3 signaling pathway by TGF-β1. Additionally, sanguiin H6 increased the expression of the epithelial marker E-cadherin and repressed the expression of Snail and the mesenchymal marker N-cadherin during TGF-β1-induced EMT. Moreover, sanguiin H6 regulated the expression of EMT-dependent genes induced by TGF-β1. Finally, sanguiin H6 inhibited the migration and invasion of TGF-β1-stimulated A549 cells. Taken together, our findings provide new evidence that sanguiin H6 suppresses lung cancer migration and invasion in vitro by inhibiting TGF-β1 induction of the EMT.

Ko H ，Jeon H ，Lee D ，Choi HK ，Kang KS ，Choi KC ... -  《-》