Green tea (−)-epigallocatechin-3-gallate inhibits HGF-induced progression in oral cavity cancer through suppression of HGF/c-Met

• Published in: The Journal of nutritional biochemistry Vol. 22; no. 11; pp. 1074 - 1083
• Main Authors: Koh, Yoon Woo, Choi, Eun Chang, Kang, Sung Un, Hwang, Hye Sook, Lee, Mi Hye, Pyun, JungHee, Park, RaeHee, Lee, YoungDon, Kim, Chul-Ho
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.11.2011; Elsevier
• Subjects: animal models; Animals; apoptosis; Biological and medical sciences; c-Met; caspase-3; Catechin - analogs & derivatives; Catechin - pharmacology; cell growth; Cell Movement - drug effects; cell proliferation; Cell Proliferation - drug effects; Chemoprevention; Disease Progression; EGCG; Feeding. Feeding behavior; Female; Fundamental and applied biological sciences. Psychology; gelatinase A; green tea; Head and neck cancer; hepatocyte growth factor; Hepatocyte Growth Factor - antagonists & inhibitors; HGF; Humans; KB Cells; Matrix Metalloproteinase 2 - biosynthesis; Matrix Metalloproteinase 9 - biosynthesis; Mice; mitogen-activated protein kinase; Mouth Neoplasms - pathology; Neoplasm Invasiveness; Oral cancer; phosphorylation; Proto-Oncogene Proteins c-met - antagonists & inhibitors; Proto-Oncogene Proteins c-met - biosynthesis; Signal Transduction - drug effects; Tea; therapeutics; Tumor invasion; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Head and neck cancer; c-Met; Oral cancer; HGF; EGCG; Tumor invasion; Stomatology; Epigallocatechin-3-gallate; Malignant tumor; Oral cavity; Vertebrata; Mammalia; ENT disease; Oral cavity disease; Green tea; Cancer
• ISSN: 0955-2863; 1873-4847
• DOI: 10.1016/j.jnutbio.2010.09.005

Hepatocyte growth factor (HGF) and c-Met have recently attracted a great deal of attention as prognostic indicators of patient outcome, and they are important in the control of tumor growth and invasion. Epigallocatechin-3-gallate (EGCG) has been shown to modulate multiple signal pathways in a manner that controls the unwanted proliferation and invasion of cells, thereby imparting cancer chemopreventive and therapeutic effects. In this study, we investigated the effects of EGCG in inhibiting HGF-induced tumor growth and invasion of oral cancer in vitro and in vivo. We examined the effects of EGCG on HGF-induced cell proliferation, migration, invasion, induction of apoptosis and modulation of HGF/c-Met signaling pathway in the KB oral cancer cell line. We investigated the antitumor effect and inhibition of c-Met expression by EGCG in a syngeneic mouse model (C3H/HeJ mice, SCC VII/SF cell line). HGF promoted cell proliferation, migration, invasion and induction of MMP (matrix metalloproteinase)-2 and MMP-9 in KB cells. EGCG significantly inhibited HGF-induced phosphorylation of Met and cell growth, invasion and expression of MMP-2 and MMP-9. EGCG blocked HGF-induced phosphorylation of c-Met and that of the downstream kinases AKT and ERK, and inhibition of p-AKT and p-ERK by EGCG was associated with marked increases in the phosphorylation of p38, JNK, cleaved caspase-3 and poly-ADP-ribose polymerase. In C3H/HeJ syngeneic mice, as an in vivo model, tumor growth was suppressed and apoptosis was increased by EGCG. Our results suggest that EGCG may be a potential therapeutic agent to inhibit HGF-induced tumor growth and invasion in oral cancer.