Epigallocatechin gallate inhibits the growth of human lung cancer by directly targeting the EGFR signaling pathway

Abstract

Epigallocatechin gallate (EGCG), the major biologically active compound in green tea, is a well-known chemoprevention agent. Although several reports have shown that EGCG exerts its anticancer activity by targeting specific cell signaling pathways, the underlying molecular mechanism(s) are only partially understood. In the present study, we report that EGCG had a profound antiproliferative effect on human lung cancer cells. EGCG inhibited anchorage-independent growth and induced cell cycle G0/G1 phase arrest. The mechanism underlying EGCG antitumor potency was mainly dependent on suppression of the EGFR signaling pathway. Short-term EGCG exposure substantially decreased EGF-induced EGFR, AKT and ERK1/2 activation. Moreover, long-term EGCG treatment not only inhibited total and membranous EGFR expression, but also markedly attenuated EGFR nuclear localization and expression of the downstream target gene cyclin D1, indicating that EGCG treatment suppressed EGFR transactivation. Additionally, knockdown of EGFR in lung cancer cells decreased their sensitivity to EGCG. Thus, inhibition of the EGFR signaling pathway may partly contribute to the anticancer activity of EGCG.

Green tea polyphenols and their potential role in health and disease

“…A down-regulation of ku70 by interrupting its binding with Bax mRNA and drug-metabolizing enzymes such as cytochrome P450 and peroxidoredoxin-V has been suggested as possible mechanism of action for cancer treatment Maliakal et al 2011;Ren et al 2011). EGCG also inhibits specific proteins with significantly altered expression level and signaling pathways such as EGFR and cell cycle in G0/ G1 phase arrest with an increase in G2M phase (Ma et al 2014). This decreases the number of cells in 'S' phase consequently suppressing tumor-promoting effect of human peptidyl prolyl cis/trans isomerase (Urusova et al 2011).…”

The Green Tea Catechin Epigallocatechin Gallate Ameliorates Graft-versus-Host Disease

“…[2, 7, 8, 12, 21] The use of EGCG in the setting of allo-HSCT is particularly interesting because of its known anti-tumor activity. EGCG is effective against a broad spectrum of tumor entities (reviewed in [22]) like colon cancer, [23] lung cancer, [24] and endometrial adenocarcinoma. [25] Numerous pathways are involved in tumor growth are affected by EGCG including suppression of NF-κB, [26] inhibition of phosphoinositide-3-kinase (PI3K), [27] Akt and STAT3 signaling, [28] down-regulation of TLR4 signal transduction, activation of 67-kDa laminin receptor (67LR) [29] and synergistic effects with anticancer drugs and micronutrients.…”

Oxidative Stress: a Promising Target for Chemoprevention

“…Enhanced expression of the genes responsible for TGF-B signaling, mediated by ROS, was evident following EGCG treatment (Lambert, Elias 2010). Furthermore, several studies have proven that it also inhibits tumor growth mediated by multi-signaling pathways - EGFR, JNK, STAT, PI3K/AKT, Wnt, or Notch (Ma et al 2014). …”

“…Studies have also shown that it reduces PSA, a well-known prostate cancer biomarker (Gunadharini et al 2006). Induction of apoptosis is related to the anti-proliferative effect of DADS mediated through the signaling pathways of EGFR, ERK, and PKM2 (Ma et al 2014), p53, p21, and MEK-ERK (Yuan et al 2015), and also by inducing cell cycle arrest.…”