A green tea polyphenol, epigalocatechin-3-gallate, induces apoptosis of human hepatocellular carcinoma, possibly through inhibition of Bcl-2 family proteins

• DOI: 10.1016/j.jhep.2005.11.045
• Publication Date: 2005-12-29T12:13:10Z
• Authors: T. Nishikawa; T. Nakajima; M. Moriguchi; M. Jo; S. Sekoguchi; M. Ishii; H. Takashima; T. Katagishi; H. Kimura; M. Minami; Y. Itoh; K. Kagawa; T. Okanoue
• Keywords: Male; 0301 basic medicine; Carcinoma, Hepatocellular; Membrane Glycoproteins; Liver Neoplasms; Administration, Oral; Down-Regulation; Apoptosis; Mice, Inbred Strains; Camellia sinensis; Catechin; 3. Good health; Enzyme Activation; TNF-Related Apoptosis-Inducing Ligand; Mice; 03 medical and health sciences; Caspases; Cell Line, Tumor; Animals; Anticarcinogenic Agents; Humans; RNA, Messenger; Apoptosis Regulatory Proteins

A major polyphenol of green tea, epigallocatechin-3-gallate (EGCG), has previously been shown to induce cell-cycle arrest and apoptosis in various cancers. However, little is known about its effects on hepatocellular carcinomas (HCCs).Four HCC cell lines, HLE, HepG2, HuH-7 and PLC/PRF/5, were treated with EGCG or vehicle. Cell viability was assessed by trypan blue staining and WST-8 assay. Cell-cycle, apoptosis and apoptosis-related proteins in HLE cells were evaluated by flow cytometry and Western blotting. The effect of EGCG was also studied in vivo using a xenograft model. The effect of co-treatment with EGCG and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) was also assessed.EGCG inhibited the growth of all HCC cell lines at concentrations of 50-100 microg/ml. In HLE cells, EGCG induced apoptosis but not cell-cycle arrest and appears to have down-regulated Bcl-2alpha and Bcl-xl by inactivation of NF-kappaB. Oral administration of EGCG showed similar effects in HLE xenograft tumors. Co-treatment with EGCG and TRAIL synergistically induced apoptosis in HLE cells.EGCG induced apoptosis in HLE cells, both in vitro and in vivo. Moreover, it enhanced TRAIL-induced apoptosis. Therefore, EGCG treatment may be useful for improving the prognosis of HCCs.