A very low toxic agent induces apoptosis and reduces growth of human hepatocellular carcinoma cells.
OBJECTIVE
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.
Schumacher
Guido
G
Department of General, Visceral, and Transplantation Surgery, Humboldt University, Charité Campus Virchow Klinikum, Berlin, Germany. guido.schumacher@charite.de
Scheunert
Sylvia
S
Rueggeberg
Anne
A
Bachem
Max G
MG
Nussler
Andreas K
AK
Spinelli
Antonino
A
Mukhopadhyay
Tapas
T
Pratschke
Johann
J
Neuhaus
Peter
P
D000077584:2-Methoxyestradiol; D017209:Apoptosis / Q000187:drug effects*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000473:pathology; D002452:Cell Count; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004958:Estradiol / Q000008:administration & dosage / Q000031:analogs & derivatives*; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology
D004958:Estradiol; D000077584:2-Methoxyestradiol