(−)-Epigallocatechin-3-gallate suppresses liver metastasis of human colorectal cancer

Abstract

(-)-Epigallocatechin-3-gallate (EGCG), the major constituent of green tea, has been shown to inhibit cell proliferation and induce apoptosis in several types of human tumors. The most common site of distant metastases in colorectal cancer is the liver. However, no previous studies have reported the ability of EGCG to suppress liver metastases of human colorectal cancer. The aim of the present study was to elucidate the potential use of EGCG as chemotherapy targeting liver metastases of human colorectal cancer. To assess the effect of EGCG on human colorectal cancer cell lines, RKO and HCT116, cell viability, cell proliferation and apoptosis were measured by cell counting kit-8, BrdU assay and TUNEL staining, respectively. Protein and gene expression were measured by western blot analysis and RT-PCR analysis, respectively. EGCG inhibited cell proliferation and induced apoptosis. EGCG dephosphorylated constitutively activated Akt and increased the activation of p38. EGCG also decreased the expression of vascular endothelial growth factor receptor 2. Additionally, the ability of EGCG to prevent the development of liver metastases of RKO tumors was evaluated in SCID mice. EGCG suppressed angiogenesis and induced apoptosis in liver metastases without associated body weight loss or hepatotoxicity. Furthermore, the liver metastatic area was significantly reduced by EGCG administration. Our findings indicate that EGCG may be useful in the treatment of liver metastases of human colorectal cancer.

Green Tea and Its Extracts in Cancer Prevention and Treatment

“…EGCG modulated multiple intracellular signaling pathways like ERK1/2, JNK1/2, p38a, p38 and AKT signaling inducing apoptosis [131], Wnt/ß-catenin pathway stimulating cell growth [28] and vascular epidermal growth factor receptor 2 [132,133]. These effects have been reported in multiple colorectal carcinoma cell cultures [134] and provide in vitro evidence for apoptosis induction, inhibition of cell growth, vascularisation and connective tissue synthesis at very high EGCG concentrations [28,[130][131][132][133][134][135].…”

“…Animal and cell culture experiments suggest specific effects of GT compounds on intracellular signaling and cell cycle control, for these studies usually the potent gallocatechin EGCG has been used. In a rat dimethylhydrazine model of colon carcinogenesis, 1% green tea as the sole drinking source lowered inflammatory cytokines like TNF-alpha, iNOS or COX-2 [128]; similarly, preneoplastic lesions in an azoxymethane-induced rat colon carcinoma model were suppressed [129], as were cell proliferation and angiogenesis in a SCID mouse model [130]. EGCG modulated multiple intracellular signaling pathways like ERK1/2, JNK1/2, p38a, p38 and AKT signaling inducing apoptosis [131], Wnt/ß-catenin pathway stimulating cell growth [28] and vascular epidermal growth factor receptor 2 [132,133].…”

“…Effective concentrations in cell culture experiments are ≥50 µmol/L [130,136], ≥20 µmol/L [28] or ≥25 µmol/L [134]. In bioavailability studies, EGCG serum concentrations rarely exceeded 1 µmol/L [136,137], making in vivo effects of EGCG extremely unlikely.…”

Green tea mechanism of action in fighting different types of cancer

“…EGCG suppressed angiogenesis and induced apoptosis in liver metastases without associated body weight loss or hepatotoxicity. Furthermore, the liver metastatic area was significantly reduced by EGCG administration (Maruyama et al, 2014). Autophagy also mediates similar effects; however, it is not currently known whether EGCG can regulate hepatic autophagy.…”

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

“…A EGCG vêm sendo considerada responsável pelo efeito protetor do chá verde por apresentar ação antioxidante (Cook e Samman, 1996;Yang et al, 1998;Anghileri e Thouvenot, 2000;Erba et al, 2005;Khan e Mukhtar, 2007;Sanna et al, 2014), antiinflamatória (Nagle et al, 2006;Bahoruna et al, 2010;Heber et al, 2014), antimicrobiana (Ikigai et al, 1993;Stapleton e Taylor, 2002;Blanco et al, 2003;Rocaro et al, 2004;Jeon et al, 2014;Lee e Tan, 2015), anticarcinogênica (Lee et al, 2009;Yang e Wang, 2010;Kang et al, 2010;Rao e Pagidas, 2010;Li et al, 2014;Maruyama et al, 2014;Butt et al, 2015), antiangiogênica (Tudoran et al, 2012;Heber et al, 2014;Koh et al, 2014), mineralizadora (Hegarty et al, 2000;Vestergaard et al, 2001;Choi et al, 2003), anti-hipertensiva (Basu e Lucas, 2007), antitumoral (Lee et al, 2009;Yang e Wang, 2010;Kang et al, 2010;Rao e Pagidas, 2010;Lemarie et al, 2013;Khan et al, 2014) e reparadora tecidual .…”