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

• Published in: Anticancer research Vol. 18; no. 3A; p. 1703
• Main Authors: Fioravanti, L, Miodini, P, Cappelletti, V, DiFronzo, G
• Format: Journal Article
• Language: English
• Published: Greece 01-05-1998
• Subjects: Anticarcinogenic Agents - pharmacology; Apoptosis - drug effects; Breast Neoplasms; Calcitriol - analogs & derivatives; Calcitriol - pharmacology; Cell Cycle - drug effects; Cell Division - drug effects; Cell Line; Cholecalciferol - analogs & derivatives; Cholecalciferol - pharmacology; Female; Growth Substances - pharmacology; Humans; Receptor, Epidermal Growth Factor - analysis; Receptor, IGF Type 1 - analysis; Receptors, Estrogen - analysis; Receptors, Progesterone - analysis; Structure-Activity Relationship; Tumor Cells, Cultured
• ISSN: 0250-7005

1,25-dihydroxycholecalciferol has been previously reported to negatively regulate human breast cancer cell growth.
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-cholec alciferol, 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.
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-a 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.
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.