Estradiol metabolites induce apoptosis in human breast cancer cells

Abstract

Certain catechol estrogens, endogenous estradiol meta-bolites, have been shown to elicit antiproliferative and antiangiogenic properties in human breast cancer cells and vascular endothelial cells at high concentrations. In the present study we investigated whether this effect can be attributed to apoptotic or cytotoxic actions. The receptor-positive (MCF-7) and the receptor-negative (MDA-MB-231) human breast cancer cell line were used. The estradiol metabolites were tested in the concentrations of 5, 10 and 20µM for 24h. Apoptosis was measured by a cell death assay and cytotoxicity using a formazan assay. In both cell lines apoptotic but no cytotoxic effects were induced by 2-OHE1, 2-OHE2, 2-MeOE1 and 2-MeOE2. In contrast 4-OHE1 and 4-OHE2 were cytotoxic. 4-MeOE1 and 4-MeOE2 did not act either apoptotic or cytotoxic. Our results indicate that catechol estrogens may be suitable for breast cancer treatment when used in high dosages. This may be of special importance for therapy, since some of these metabolites have been shown to be tolerated much better than cytostatics, even in high dosages. In addition, some elicit only low estrogenic activity in terms of the reproductive system.