FACS analysis of oxidative stress induced on tumour cells by SERMs

This study confirms previous reports of the antiproliferative effect of OH-ferrocifen on both hormone-dependent MCF-7 and hormone-independent MDA-MB-231 breast cancer cell models. Contrastive analysis of the proliferative effects of classical agonists (including estradiol and ethynylestradiol) and selective estrogen receptor modulators (SERMs) such as tamoxifen and its active metabolite, 4-hydroxy-tamoxifen, was also performed. Previous studies have attributed the effects of OH-ferrocifen on hormone-independent cells to an underlying mechanism based on intracellular oxidation, production of hydroxyl radicals and oxidative damage of DNA. Here we report that the chemically generated OH-ferrocifen cation (as well as the decamethylferrocenium cation) is less cytotoxic to both cell lines than the neutral parent complex. Moreover, fluorescence activated cell sorting (FACS) analysis of 8-oxo-guanine production indicates that, even at relatively high concentrations, OH-ferrocifen produces negligible oxidative DNA damage as compared to other SERMs, namely tamoxifen and 4-hydroxy-tamoxifen. Alternative pathways to explain the remarkable activity of OH-ferrocifen must therefore be sought.