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.