Antiestrogenic effects of Z-1, 1-dichloro-2,3 diphenyl-2-(4-methoxyphenyl)cyclopropane(5a) on human breast cancer cells in culture.

Compound 5a ([Z]-1, 1-Dichloro-2,3 diphenyl-2-(4-methoxyphenyl)cyclopropane) is a novel cyclopropyl compound which was shown to be a pure antiestrogen. In the present study, the antiproliferative activity of 5a was examined on estrogen receptor (ER)-positive MCF-7 and ER-negative MDA-MB-231 human breast cancer cells and A-549 human lung cancer cells using the hemocytometric trypan blue exclusion method. Compound 5a inhibited the growth of MCF-7 cells in a dose-related manner over a concentration range of 10(-9) to 10(-5) M, but did not alter the growth of MDA-MB-231 or A-549 cells. Co-administration of estradiol (10(-8) M) reversed the antiproliferative activity of 5a (10(-7) M) on MCF-7 cells. Further, an ER-dependent mechanism of action is supported by the specific ER binding of 5a in MCF-7 cells observed in this study. The influence of 5a on the cell surface morphology of MCF-7 and MDA-MB-231 cells was studied using scanning electron microscopy (SEM). Compound 5a at 10(-6) M reduced the length and density of microvilli (MV) on MCF-7 cells, which was reversed by co-administration of estradiol (10(-8) M). This compound did not alter the cell surface morphology of ER-negative MDA-MB-231 cells. In conclusion, 5a and tamoxifen inhibited the growth of ER-prositive MCF-7 cells in an estradiol-reversible manner, and had no effect on ER-negative MDA-MB-231 cells. The results of this study with human breast cancer cells suggest that 5a may be highly effective in the treatment of estrogen-dependent breast cancer and/or in the prophylactic treatment of women with a high risk of breast cancer development.
AuthorsP T Jain, J T Pento, R A Magarian
JournalAnticancer research (Anticancer Res) 1992 May-Jun Vol. 12 Issue 3 Pg. 585-90 ISSN: 0250-7005 [Print] GREECE
PMID1622114 (Publication Type: Comparative Study, Journal Article)
Chemical References
  • Estrogen Antagonists
  • Receptors, Estrogen
  • Tamoxifen
  • 1,1-dichloro-2,3-diphenyl-2-(4-methoxyphenyl)cyclopropane
  • Estradiol
  • Breast Neoplasms
  • Cell Division (drug effects)
  • Cell Line
  • Cell Membrane (drug effects, ultrastructure)
  • Dose-Response Relationship, Drug
  • Estradiol (metabolism, pharmacology)
  • Estrogen Antagonists (pharmacology)
  • Female
  • Humans
  • Kinetics
  • Microscopy, Electron, Scanning
  • Receptors, Estrogen (metabolism)
  • Tamoxifen (analogs & derivatives, metabolism, pharmacology)
  • Tumor Cells, Cultured

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research network!

Choose Username:
Verify Password:
Type Validation Code Shown: