Estradiol metabolites are potent mitogenic substances for human ovarian cancer cells

Purpose of investigation: The etiology of ovarian cancer appears to be associated with a long-term influence of estrogens. However, evidence is accumulating that certain estradiol metabolites may play a decisive role in the carcinogenesis of estrogen-dependent diseases. In the present study we examined the effect of estradiol metabolites on the proliferation and apoptosis of human ovarian cancer cells in comparison to the effect of their parent substance.

Methods: The ovarian cancer cell line OVCAR-3 was used for the experiments. 17Beta-estradiol (E2), 2-hydroxyestradiol (2-OHE2), 4-hydroxyestradiol (4-OHE2) and 16alpha-hydroxyestrone (16-OHE1) were incubated for seven days in the concentration range of 0.01 nM to 10 nM. Proliferation and apoptosis were measured by commercially available assay kits.

Results: E2 enhanced proliferation rate and concomitantly reduced apoptotic rate of the ovarian cancer cells at physiological concentrations. 2-OHE2 had no significant effect, whereas 4-OHE2 elicited similar effects on proliferation and apoptotic rate as E2. The greatest proliferative and antiapoptotic effect was observed for 16-OHE1, the values being significantly different to the effects of E2.

Conclusion: The pattern of endogenous estradiol metabolism may play a role in defining ovarian cancer risk. This may be of importance in certain predisposed women who are treated with hormone therapy in postmenopause.

Estradiol metabolites; Ovarian cancer cells; Proliferation

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