Aim: The study was designed to examine the potential cytotoxicity of 2-methoxyestradiol (2ME2), a natural 17β-estradiol metabolite, in hepatocellular carcinoma and the possible underlying mechanisms for this cytotoxicity. Methods: The cell line HepG2 was treated with different concentrations of 2ME2 for 48 and 72 h. Results: Using the sulforhodamine B assay, HepG2 was sensitive to the cytotoxic effect of 2ME2. 2ME2 induced cell arrest at the G2/M phase and a significant high percentage of apoptotic cells compared to the control group. Also, 2ME2 induced a significant increase in caspase 9 enzymatic activity after 48 and 72 h of treatment compared with control values. The DNA laddering was observed only in cells treated for 72 h. Furthermore, 2ME2 induced a significant decrease in the expression levels of vascular endothelial growth factor (VEGF) gene compared to the control values. Conclusion: 2ME2 exerts cytotoxic activity in the HepG2 cell line by preferential cell blocking at the G2/M phase as well as induction of apoptosis as evidenced by increased caspase 9 enzymatic activity and observed DNA laddering in 2ME2-treated HepG2 cells. In addition, a reduction in hypervascularity is an important postulated mechanism as indicated by the significant reduction in the expression of VGEF, one of the most important angiogenic factors.

Keywords:
2-Methoxyestradiol, Hepatocellular carcinoma, Apoptosis, Angiogenesis
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© 2009 S. Karger AG, Basel
2009
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