title: Influence of cyclopropyl antiestrogens on the cell cycle kinetics of MCF-7 human breast cancer cells.
abstract: 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.
authors.affiliation: Department of Pharmacology and Toxicology, College of Pharmacy, University of Oklahoma Health Sciences Center, Oklahoma City 73190, USA.
authors.forename: P T
authors.initials: PT
authors.lastname: Jain
authors.forename: J T
authors.initials: JT
authors.lastname: Pento
authors.forename: R A
authors.initials: RA
authors.lastname: Magarian
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology*; D018931:Antineoplastic Agents, Hormonal / Q000737:chemistry / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000473:pathology*; D002453:Cell Cycle / Q000187:drug effects*; D003521:Cyclopropanes / Q000737:chemistry / Q000494:pharmacology*; D004273:DNA, Neoplasm / Q000032:analysis; D004958:Estradiol / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000737:chemistry / Q000494:pharmacology*; D004967:Estrogens; D005260:Female; D006801:Humans; D009376:Neoplasms, Hormone-Dependent / Q000473:pathology*; D013629:Tamoxifen / Q000494:pharmacology; D014407:Tumor Cells, Cultured
chemical_list: D018931:Antineoplastic Agents, Hormonal; D003521:Cyclopropanes; D004273:DNA, Neoplasm; D004965:Estrogen Antagonists; D004967:Estrogens; D013629:Tamoxifen; D004958:Estradiol