EGCG Inhibits Proliferation, Invasiveness and Tumor Growth by Up-Regulation of Adhesion Molecules, Suppression of Gelatinases Activity, and Induction of Apoptosis in Nasopharyngeal Carcinoma Cells

Abstract

(−)-Epigallocatechin-3-gallate (EGCG), a major green tea polyphenol, has been shown to inhibit the proliferation of a variety of tumor cells. Epidemiological studies have shown that drinking green tea can reduce the incidence of nasopharyngeal carcinoma (NPC), yet the underlying mechanism is not well understood. In this study, the inhibitory effect of EGCG was tested on a set of Epstein Barr virus-negative and -positive NPC cell lines. Treatment with EGCG inhibited the proliferation of NPC cells but did not affect the growth of a non-malignant nasopharyngeal cell line, NP460hTert. Moreover, EGCG treated cells had reduced migration and invasive properties. The expression of the cell adhesion molecules E-cadherin and β-catenin was found to be up-regulated by EGCG treatment, while the down-regulation of matrix metalloproteinases (MMP)-2 and MMP-9 were found to be mediated by suppression of extracellular signal-regulated kinase (ERK) phosphorylation and AP-1 and Sp1 transactivation. Spheroid formation by NPC cells in suspension was significantly inhibited by EGCG. Oral administration of EGCG was capable of suppressing tumor growth in xenografted mice bearing NPC tumors. Treatment with EGCG was found to elevate the expression of p53 and p21, and eventually led to apoptosis of NPC cells via caspase 3 activation. The nuclear translocation of NF-κB and β-catenin was also suppressed by EGCG treatment. These results indicate that EGCG can inhibit the proliferation and invasiveness, and induce apoptosis, of NPC cells, making it a promising agent for chemoprevention or adjuvant therapy of NPC.

RETRACTED ARTICLE: Physcion, a naturally occurring anthraquinone derivative, induces apoptosis and autophagy in human nasopharyngeal carcinoma

“…The role of Sp1 in apoptosis has been well documented in a number of cancer cells, including nasopharyngeal carcinoma [37,38] . Interestingly, a recent study by Yang et al found that downregulated expression of Sp1 was associated with induction of autophagy in the human myeloid leukemia cell line K-562 [39] .…”

Modeling nasopharyngeal carcinoma in three dimensions

“…One of the disadvantages of the 3D spheroid model is the lack of tumor complexity, which can be overcome by the increase in the range and convolution of models applicable to researchers including co-culture system and patient-derived spheroids (67,68). Although we have the capability to recreate the tumor microenvironment architecture with a matrix of the 3D cell culture, variability in the matrix, particularly ones that are biologically derived, may yield non-reproducible results.…”

“…A number of previous studies have developed improved NPC models based on spheroid cultures; these have increased in number due to novel culture methods emerging from the field of tissue engineering (Table I) (8,42,43,67,. Formerly, the utilization of ultra-low attachment plates and hanging drop were the most common methods used to generate spheroids from NPC cells (74).…”

Formulação à base de Epigalocatequina-3-galato, derivada do chá verde, desenvolvida para uso endodôntico: estudo físico-químico e biológico

“…A EGCG, uma das catequinas isoladas e purificadas a partir do chá-verde, avaliada no presente estudo, tornou-se uma das substâncias naturais mais estudadas atualmente, sendo a principal responsável pelos efeitos biológicos que resultam na prevenção e tratamento de diferentes doenças (Yun et al, 2007;Yang et al, 2010;Hodgson e Croft, 2010;Prabhakar et al, 2010;Rao e Pagidas, 2010;Yang e Wang, 2010;Rodriguez et al, 2011;Subramaniam et al, 2012;Jung et al, 2012;Cai et al, 2013;Wierzejska, 2014;Fang et al, 2015;Tenore et al, 2015).…”

“…O chá verde é uma das bebidas mais populares em todo o mundo e tem recebido atenção especial por apresentar comprovados efeitos na saúde geral (Chung et al, 2001;Pianetti et al, 2002;Chung et al, 2003;Dreger et al, 2008;Lee et al, 2009;Hodgson e Croft, 2010;Prabhakar et al, 2010;Rao e Pagidas, 2010;Yang e Wang, 2010;Subramaniam et al, 2012;Jung et al, 2012;Cai et al, 2013;Wierzejska, 2014;Fang et al, 2015;Tenore et al, 2015). Seus principais componentes químicos são flavonóides e catequinas, que correspondem a aproximadamente 26,7% do seu conteúdo.…”