Epigallocatechin gallate (EGCG) suppresses epithelial-Mesenchymal transition (EMT) and invasion in anaplastic thyroid carcinoma cells through blocking of TGF-β1/Smad signaling pathways

Decades of research have enabled us to develop a better and sharper understanding of multifaceted nature of cancer. Next-generation sequencing technologies have leveraged our existing knowledge related to intra- and inter-tumor heterogeneity to the next level. Functional genomics have opened new horizons to explore deregulated signaling pathways in different cancers. Therapeutic targeting of deregulated oncogenic signaling cascades by products obtained from natural sources has shown promising results. Epigallocatechin-3-gallate (EGCG) has emerged as a distinguished chemopreventive product because of its ability to regulate a myriad of oncogenic signaling pathways. Based on its scientifically approved anticancer activity and encouraging results obtained from preclinical trials, it is also being tested in various phases of clinical trials. A series of clinical trials associated with green tea extracts and EGCG are providing clues about significant potential of EGCG to mechanistically modulate wide ranging signal transduction cascades. In this review, we comprehensively analyzed regulation of JAK/STAT, Wnt/β-catenin, TGF/SMAD, SHH/GLI, NOTCH pathways by EGCG. We also discussed most recent evidence related to the ability of EGCG to modulate non-coding RNAs in different cancers. Methylation of the genome is also a widely studied mechanism and EGCG has been shown to modulate DNA methyltransferases (DNMTs) and protein enhancer of zeste-2 (EZH2) in multiple cancers. Moreover, the use of nanoformulations to increase the bioavailability and thus efficacy of EGCG will be also addressed. Better understanding of the pleiotropic abilities of EGCG to modulate intracellular pathways along with the development of effective EGCG delivery vehicles will be helpful in getting a step closer to individualized medicines.

Section: Tgf/smad Signalingmentioning

confidence: 92%

Section: Tgf/smad Signalingmentioning

confidence: 99%

EGCG Mediated Targeting of Deregulated Signaling Pathways and Non-Coding RNAs in Different Cancers: Focus on JAK/STAT, Wnt/β-Catenin, TGF/SMAD, NOTCH, SHH/GLI, and TRAIL Mediated Signaling Pathways

Farooqi

Pinheiro

Granja

et al. 2020

“…Epigallocatechin gallate (EGCG), a compound extracted from green tea, has been proven to have multiple anticancer, anti-inflammatory, anti-EMT, and anti-oxidant proprieties [145][146][147]. Despite its ability to act as an excellent anticancer drug, EGCG displays some limitations related to stability, bioavailability, and metabolic conversion under physiological conditions [148,149].…”

Section: Epigallocatechin Gallatementioning

confidence: 99%

Nanomaterials as Inhibitors of Epithelial Mesenchymal Transition in Cancer Treatment

Cordani

Strippoli

Somoza

2019

Epithelial-mesenchymal transition (EMT) has emerged as a key regulator of cell invasion and metastasis in cancers. Besides the acquisition of migratory/invasive abilities, the EMT process is tightly connected with the generation of cancer stem cells (CSCs), thus contributing to chemoresistance. However, although EMT represents a relevant therapeutic target for cancer treatment, its application in the clinic is still limited due to various reasons, including tumor-stage heterogeneity, molecular-cellular target specificity, and appropriate drug delivery. Concerning this last point, different nanomaterials may be used to counteract EMT induction, providing novel therapeutic tools against many different cancers. In this review, (1) we discuss the application of various nanomaterials for EMT-based therapies in cancer, (2) we summarize the therapeutic relevance of some of the proposed EMT targets, and (3) we review the potential benefits and weaknesses of each approach.

“…Epigallocatechin-3-gallate (25-50 µM) can also suppress nicotine-induced migration and invasion by blocking angiogenesis and EMT of non-small cell lung carcinoma (NSCLC) cells [158]. It (10-60 µM) also suppresses EMT and invasion in anaplastic thyroid carcinoma cells by blocking TGF-1/Smad pathways [159].…”

Section: Reversal Of Emt By Anti-inflammatory Natural Compoundsmentioning

confidence: 99%

Reversal of Epithelial–Mesenchymal Transition by Natural Anti-Inflammatory and Pro-Resolving Lipids

Lee

2019

Epithelial mesenchymal transition (EMT) is a key process in the progression of malignant cancer. Therefore, blocking the EMT can be a critical fast track for the development of anticancer drugs. In this paper, we update recent research output of EMT and we explore suppression of EMT by natural anti-inflammatory compounds and pro-resolving lipids.A typical signaling pathway of EMT is the transforming growth factor-β1 (TGF-β1) pathway. TGF-β1 induces EMT via SMAD-dependent or non-SMAD signaling pathway [7]. Growth factors including FGF, HGF, IGF1, EGF, and PDGF via receptor tyrosine kinase can induce EMT via signaling pathway of PI3K-AKT and ERK MAPK [8][9][10][11]. Wnt signaling, hedgehog signaling, Notch signaling, hypoxia, and inflammatory tumor microenvironment also involves in EMT [5]. Recently, it has been shown that hippo signaling is also involved in EMT [12]. YAP and TAZ can enhance EMT through upregulation of EMT transcription factors such as forkhead box C2 (FOXC2), snail family zinc finger 1/2 (SNAIL1, SLUG), twist-related protein 1 (TWIST1), and ZEB1 [12-15]. Transcription Factors Involved in EMTNovel players are newly recognized as regulatory transcription factor in the EMT. Brachyury, the T-box transcription factor, is a novel transcription factor implicated in the EMT of cancer cells [16]. Brachyury is known as the target gene of WNT, one of the m ajor signaling pathways of EMT [17]. Foxq1, one of forkhead transcription factor, has also regarded as a novel transcription factor mediating the EMT of gastric cancer [6,18]. Runt-related transcription factor 2 (Runx2) belongs to the runt-related transcription factor family [19]. Runx2 plays a key role in EMT of hepatocellular carcinoma (HCC) [20]. GATA transcription factors are also implicated in the EMT of cancer cells [21].A typical signaling pathway of EMT is the transforming growth factor-β1 (TGF-β1) pathway. TGF-β1 induces EMT via SMAD-dependent or non-SMAD signaling pathway [7]. Growth factors including FGF, HGF, IGF1, EGF, and PDGF via receptor tyrosine kinase can induce EMT via signaling pathway of PI3K-AKT and ERK MAPK [8][9][10][11]. Wnt signaling, hedgehog signaling, Notch signaling, hypoxia, and inflammatory tumor microenvironment also involves in EMT [5]. Recently, it has been shown that hippo signaling is also involved in EMT [12]. YAP and TAZ can enhance EMT through upregulation of EMT transcription factors such as forkhead box C2 (FOXC2), snail family zinc finger 1/2 (SNAIL1, SLUG), twist-related protein 1 (TWIST1), and ZEB1 [12-15]. Transcription Factors Involved in EMTNovel players are newly recognized as regulatory transcription factor in the EMT. Brachyury, the T-box transcription factor, is a novel transcription factor implicated in the EMT of cancer cells [16]. Brachyury is known as the target gene of WNT, one of the major signaling pathways of EMT [17]. Foxq1, one of forkhead transcription factor, has also regarded as a novel transcription factor mediating the EMT of gastric cancer [6,18]. Runt-related transcription factor 2 (Runx2...