Influence of cyclopropyl antiestrogens on the cell cycle kinetics of MCF-7 human breast cancer cells.

Five cyclopropyl compounds, previously shown to exhibit pure antiestrogenic activity in the mouse uterotropic assay and antiproliferative activity of MCF-7 human breast cancer cells in culture, were examined for their influence on the cell cycle kinetics of MCF-7 cells. The DNA-histogram of a single cell suspension was obtained on Coulter Epics V after fixing the cells in 70 % ethyl alcohol and staining in propidium iodide. Tamoxifen increased the percentage of cells in G1-phase with a concomitant decrease in percentage of cells in S-phase, in an estradiol reversible manner. Cyclopropyl compound 7a increased the percentage of cells in G1-phase, in an estradiol-irreversible manner. Further, compounds 5a, 5c, 7a and 7b decreased the percentage of cells in S-phase and increased percentage of cells in the G2M-phase, in an estradiol-irreversible manner. Of the five cyclopropyl compounds tested, only 4d had no influence on the cytokinetic parameters, even though this compound was found to exhibit antiproliferative activity on MCF-7 cells equal to that of tamoxifen. In conclusion, all of the cyclopropyl compounds, except 4d, altered cell cycle parameters of MCF-7 cells in a manner different than that of tamoxifen. Thus, the results of this study indicate that, although these cyclopropyl compounds are antiestrogenic, they produce antiproliferative activity by a distinct mechanism of action in estrogen receptor positive breast cancer cells.