EGCG Inhibits Transforming Growth Factor-β-Mediated Epithelial-to-Mesenchymal Transition via the Inhibition of Smad2 and Erk1/2 Signaling Pathways in Nonsmall Cell Lung Cancer Cells

Abstract

Transforming growth factor-β (TGF-β)-mediated epithelial mesenchymal transition (EMT) of human lung cancer cells may contribute to lung cancer metastasis. It has been reported that EGCG can inhibit tumorigenesis and cancer cell growth in lung cancer; however, the effect of EGCG on EMT in nonsmall cell lung cancer (NSCLC) cells has not been investigated. In this study, we found that NSCLC cells A549 and H1299 were converted to the fibroblastic phenotype in response to TGF-β. Epithelial marker E-cadherin was down-regulated, and mesenchymal marker vimentin was up-regulated simultaneously. Our results illustrated that TGF-β was able to induce EMT in NSCLC cells, and EGCG would reverse TGF-β-induced morphological changes, up-regulate the expression of E-cadherin, and down-regulate the expression of vimentin. Immunofluorescent staining also demonstrated that E-cadherin was up-regulated and that vimentin was down-regulated by EGCG pretreatment. Moreover, wound-healing and the in vitro invasion assay showed that EGCG could inhibit TGF-β-induced migration and invasion of NSCLC cells. By using the dual-luciferase reporter assay, we demonstrated that EGCG inhibited TGF-β-induced EMT at the transcriptional level. EGCG decreased the phosphorylation of Smad2 and Erk1/2, inhibited the nuclear translocation of Smad2, and repressed the expression of transcription factors ZEB1, Snail, Slug, and Twist, and up-regulated the expression of E-cadherin. In summary, our results suggest that EGCG can inhibit TGF-β-induced EMT via down-regulation of phosphorylated Smad2 and Erk1/2 in NSCLC cells.

YXQ-EQ Induces Apoptosis and Inhibits Signaling Pathways Important for Metastasis in Non-Small Cell Lung Carcinoma Cells

“…TGF-β induced EMT increases the potential for tumor metastasis by enhancing motility and invasion of cancer cells [30,49]. TGF-β induces EMT in cancer cells including A549 cells by activating SMAD2/3, AKT, and ERK1/2 [33,[50][51][52]. Inhibition of TGF-β/SMAD signaling by YXQ-EQ reported here suggests that YXQ-EQ may also exert antitumor effects by inhibiting the pro-tumor activities of TGF-β.…”

A derivative of epigallocatechin‐3‐gallate induces apoptosis via SHP‐1‐mediated suppression of BCR‐ABL and STAT3 signalling in chronic myelogenous leukaemia

“…Similarly, EGCG from green tea has been shown to exert potent anti-tumour activity in several types of leukaemia (Lung et al, 2002;Lee et al, 2004), prostate cancer (Siddiqui et al, 2011;Lee et al, 2012), cervical cancer (Ahn et al, 2003), colon cancer (Shimizu et al, 2005), lung cancer (Milligan et al, 2009;Wang et al, 2011;Liu et al, 2012), breast cancer (Sen and Chatterjee, 2011) and pancreatic cancer (Tang et al, 2012). However, clinical application of EGCG has been hampered by its limited solubility and efficacy in patients with cancer, underlining the need for the development of potent EGCG derivatives with improved metabolic stability and greater anti-cancer efficacy.…”

Withaferin a synergistically enhances the effects of paclitaxel against lung cancer.

“…In agreement with previous studies [62,74], we successfully used 5 ng/mL TGFβ1 in serum-free media to induce EMT in H1299 and A549 NSCLC cells. Our findings indicate the TGFβ1 decreased the expression of E-cadherin in both A549…”