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

J Hepatol. 2006 Jun;44(6):1074-82. doi: 10.1016/j.jhep.2005.11.045. Epub 2005 Dec 28.


Background/aims: 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).

Methods: 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.

Results: 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.

Conclusions: 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.

MeSH terms

  • Administration, Oral
  • Animals
  • Anticarcinogenic Agents / analysis
  • Anticarcinogenic Agents / therapeutic use*
  • Apoptosis
  • Apoptosis Regulatory Proteins / therapeutic use
  • Camellia sinensis / chemistry
  • Carcinoma, Hepatocellular / drug therapy*
  • Carcinoma, Hepatocellular / metabolism
  • Caspases / metabolism
  • Catechin / analogs & derivatives*
  • Catechin / analysis
  • Catechin / therapeutic use
  • Cell Line, Tumor
  • Down-Regulation
  • Enzyme Activation
  • Humans
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / metabolism
  • Male
  • Membrane Glycoproteins / therapeutic use
  • Mice
  • Mice, Inbred Strains
  • RNA, Messenger / analysis
  • RNA, Messenger / metabolism
  • TNF-Related Apoptosis-Inducing Ligand
  • Tea / chemistry
  • Tumor Necrosis Factor-alpha / therapeutic use
  • Xenograft Model Antitumor Assays
  • bcl-2-Associated X Protein / genetics
  • bcl-2-Associated X Protein / metabolism*
  • bcl-X Protein / genetics
  • bcl-X Protein / metabolism*


  • Anticarcinogenic Agents
  • Apoptosis Regulatory Proteins
  • Membrane Glycoproteins
  • RNA, Messenger
  • TNF-Related Apoptosis-Inducing Ligand
  • TNFSF10 protein, human
  • Tea
  • Tnfsf10 protein, mouse
  • Tumor Necrosis Factor-alpha
  • bcl-2-Associated X Protein
  • bcl-X Protein
  • Catechin
  • epigallocatechin gallate
  • Caspases