A very low toxic agent induces apoptosis and reduces growth of human hepatocellular carcinoma cells.

AIM: To examine the efficacy on growth inhibition of 2-methoxyestradiol (2-ME) on human hepatocellular carcinoma in vitro. METHODS: Hep3B, SK-Hep1, and PLC/PRF/5 cells were used. Proliferation assays using 2-ME should show a dose-dependent reduction of cell number. Different staining methods in cells derived from human hepatocellular carcinoma and normal human hepatocytes were performed to demonstrate possible tumor specific induction of apoptosis. FACS-analysis was done to confirm the induction of apoptosis after treatment with 2-ME. RESULTS: A reduction of the cell number of 90-98% was observed in all cancer cells after treatment with 2 micromol 2-ME. The mechanism of action appeared to be induction of apoptosis. Normal human hepatocytes were unaffected by 2-ME. The most sensitive cell line to 2-ME, SK-Hep1, showed an up-regulation of the p53 and p21 proteins. CONCLUSIONS: 2-Methoxyestradiol appears to be highly effective in reducing tumor growth in vitro in human hepatocellular carcinoma. It may be tumor specific and applicable for clinical trials.