title: (-)-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.
authors: Department of Surgery, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan.
authors: Takehito
authors: T
authors: Maruyama
authors: Department of Surgery, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan.
authors: Soichiro
authors: S
authors: Murata
authors: Department of Surgery, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan.
authors: Ken
authors: K
authors: Nakayama
authors: Department of Surgery, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan.
authors: Naoki
authors: N
authors: Sano
authors: Department of Surgery, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan.
authors: Koichi
authors: K
authors: Ogawa
authors: Department of Surgery, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan.
authors: Takeshi
authors: T
authors: Nowatari
authors: Department of Surgery, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan.
authors: Takafumi
authors: T
authors: Tamura
authors: Department of Surgery, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan.
authors: Reiji
authors: R
authors: Nozaki
authors: Department of Surgery, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan.
authors: Kiyoshi
authors: K
authors: Fukunaga
authors: Department of Surgery, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan.
authors: Nobuhiro
authors: N
authors: Ohkohchi
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D004789:Enzyme Activation / Q000187:drug effects; D045325:HCT116 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy / Q000517:prevention & control* / Q000556:secondary; D008297:Male; D051379:Mice; D016513:Mice, SCID; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000096:biosynthesis; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D016588:Anticarcinogenic Agents; D000975:Antioxidants; D002392:Catechin; C045651:epigallocatechin gallate; C000588866:KDR protein, human; D040301:Vascular Endothelial Growth Factor Receptor-2; D051057:Proto-Oncogene Proteins c-akt; D048051:p38 Mitogen-Activated Protein Kinases