Synthetic analogs of vitamin D3 have inhibitory effects on breast cancer cell lines

L. Fioravanti, P. Miodini, V. Cappelletti, G. Di Fronzo

Research output: Contribution to journalArticle

Abstract

Background: 1,25-dihydroxycholecalciferol has been previously reported to negatively regulate human breast cancer cell growth. Material and methods: The antiproliferative effect of 1,25-dihydroxycholecalciferol (Ro 21-5535) and of the two non hypercalcemic analogs (1a,25-dihydroxy-16-ene-23-yne-26,27-hexafluorocholecalciferol, Ro 24-5531 and 1a,25-dihydroxy-16-ene-23-yne-26,27-hexafluoro-19-nor-cholecalciferol, Ro 25-6760) was studied in MCF-7 and MDAMB-468 human breast cancer cell lines. Cell cycle distribution and apoptosis were evaluated by flow cytometry. Steroid receptor modulation was investigated by radioligand assay. Results: The most effective drug was the Ro 25-6760 which at concentrations ranging between 1-100 nM caused a dose dependent growth inhibition apparently due to accumulation in G0/G1. Vitamin D3 analogs (10 nM) significantly counteracted the growth stimulation induced by TGF-α and IGF-I as well as the paracrine stimulation observed in co- cultures. They antagonized estradiol-promoted growth stimulation and progestrone receptor induction in MCF-7 cells. Conclusion: Vitamin D3 analogs represent a class of clinically attractive drugs for treatment of breast cancer due to their ability to counteract estradiol and growth factor-induced growth stimulation.

Original languageEnglish
Pages (from-to)1703-1708
Number of pages6
JournalAnticancer Research
Volume18
Issue number3 A
Publication statusPublished - May 1998

Keywords

  • Breast cancer
  • Synthetic analogs
  • Vitamin D

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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