Proliferative Properties of 17β-aminoestrogens in MCF-7 Human Breast Cancer Cells

The 17β-aminoestrogens (AEs) prolame, butolame and pentolame are weakly oestrogenic in rodents and display anticoagulant properties in contrast to oestradiol (E₂ ) which presents pro-coagulant effects, potentially thrombogenic. They possess anti-anxiety and antidepressive properties, being good candidates for menopausal hormone therapy (MHT). Their capability to induce proliferation of MCF-7 human breast cancer cells, in which proliferative rate depends on oestrogens, has not been explored; thus, the aim of this work was to characterize it. AEs' proliferation properties were evaluated compared with E₂ in MCF-7 carcinoma cell line cultures using established methods. Receptor mediation on cell proliferation was studied by co-incubating them with the oestrogen receptor antagonists tamoxifen, ICI 182,780 and the selective antagonists MPP (ERα) and PHTPP (ERβ). E₂ and AEs increased MCF-7 cell proliferation; their proliferative effect was between 1.5-2 and E₂ = 3.6 compared with controls (0); their relative proliferative effect was 18-38% (E₂ = 100%) with a relative proliferative potency of 4.5-8.9 (E₂ = 100). The ERα antagonist MPP inhibited the MCF-7 cell proliferation induced by E₂ and AEs; on the contrary, the ERβ antagonist PHTPP exacerbated the proliferative response, showing that the AEs' proliferative activity was mainly ERα-mediated and apparently controlled by ERβ. Preliminary cytometric DNA flow analysis showed that AEs' cell cycle S phase inducer property was lower than E₂ following the proliferative order: E₂ > butolame > prolame > pentolame, indicating pentolame with the weakest proliferative properties and being the safest of this series as a candidate for MHT.