Anti-metastatic and differential effects on protein expression of epigallocatechin-3-gallate in HCCLM6 hepatocellular carcinoma cells

Abstract

Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and the third highest cause of cancer-related mortality in humans. Epigallocatechin-3-gallate (EGCG) has been shown to inhibit the metastatic activity of certain cancer cells. The aim of this study was to determine the effects and molecular mechanism(s) of action of EGCG in human HCC cells. A migration and invasion assay for the metastatic behavior of HCCLM6 cells was performed. The anti-metastatic effects of EGCG were investigated by RT-PCR and gelatin zymography. A total cellular protein profile was obtained using 2-dimensional gel electrophoresis (2-DE), followed by matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF-MS) analyses of proteins with significant differences in expression following treatment with EGCG. The results revealed that EGCG induced apoptosis and inhibited the metastasis of HCCLM6 cells. The anti-metastatic effects of EGCG were associated with the inhibition of matrix metalloproteinase (MMP)-2 and MMP-9 activity. The expression levels of far upstream element (FUSE) binding protein 1 (FUBP1), heat shock protein beta 1 (HSPB1), heat shock 60 kDa protein 1 (chaperonin) (CH60) and nucleophosmin (NPM) proteins, which are associated with metastasis, were significantly altered in the EGCG-treated HCCLM6 cells. The data from the present study suggest that EGCG has potential as a therapeutic agent for the treatment of HCC.

Anticancer activities of epigallocatechin-3-gallate against cholangiocarcinoma cells

“…Furthermore, it dose-dependently inhibits MMP-2 activity, which is a major enzyme for the invasion process, and migration of HuCC-T1 cells as shown in Figure 3. Zhang et al also reported that EGCG efficiently inhibits MMP-2/9 activity and invasion of hepatocellular carcinoma cells 28,29. Furthermore, they also reported that EGCG has no adverse effects against non-cancerous liver cells.…”

Epigallocatechin-3-gallate inhibits cell growth, induces apoptosis and causes S phase arrest in hepatocellular carcinoma by suppressing the AKT pathway

“…EGCG also delayed HCC cell growth through inhibition of Bcl-2 family (16,19) or induced apoptosis in HCC cells via downregulation of COX-2 and Bcl-2, and consequently activated caspase-9 and caspase-3 (31). The anti-metastatic effects of EGCG were associated with the inhibition of MMP-2 and MMP-9 activity (32,33).…”

Epigallocatechin‐3‐gallate ameliorates intrahepatic cholestasis of pregnancy by inhibiting matrix metalloproteinase‐2 and matrix metalloproteinase‐9

“…For instance, in breast cancer patients under radiotherapy, EGCG administration was shown to significantly reduce activation of both MMP‐2 and MMP‐9 . In addition, in cell lines of human sarcoma and hepatocellular carcinoma, EGCG was consistently found to inhibit cancer cell growth by repressing activities of both MMP‐2 and MMP‐9 , while in ovarian carcinoma cells, EGCG was also able to downregulate MMP‐2 .…”

“…EGCG reduced levels of both MMP-2 and MMP-9 in a post-transcriptional manner in ICP rats Various studies have demonstrated that EGCG functions to repress activities of both MMP-2 and MMP-9 [25][26][27][28], we therefore are curious whether EGCG could exert the same function in the EE-induced rat ICP model. Following the initial 5 days of EE treatment, further administration of EGCG at 20 mg/kg of body weight daily by oral gavage for five consecutive days was conducted on the ICP rats (ICP+EGCG group), and rats treated with EE at the same pregnancy stage served as control (ICP group).…”

“…Matrix metalloproteinases (MMPs), a type of enzymes that degrade the extracellular matrix, are secreted by the placental cells during remodeling of tissues, specifically MMP-2 and MMP-9, and have often been linked to many diseases in pregnancy such as fetal inflammatory response, preterm labor [20], peripartum cardiomyopathy [21], pre-eclampsia [22,23] and ICP [24]. Epigallocatechin-3-gallate (EGCG), a major catechin extracted from green tea, has been reported to repress MMP-2 and MMP-9 in various researches [25][26][27][28]. Therefore in the current study, we investigated whether EGCG could exert the same inhibitory functions toward the two MMPs in a rat ICP model induced by ethinylestradiol.…”