Vitamin D analogues suppress IGF-I signalling and promote apoptosis in breast cancer cells

Eur J Cancer. 1999 Nov;35(12):1717-23. doi: 10.1016/s0959-8049(99)00200-2.


Survival factors are known to promote cell viability, and factor deprivation can be a potent apoptotic signal. Insulin-like growth factors are potent mitogens and inhibitors of apoptosis for many normal and neoplastic cells with insulin-like growth factor-I (IGF-I) being the most effective in many breast cancer cell lines. 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) and its analogues inhibit IGF-I-stimulated growth of MCF-7 human breast cancer cells. The aim of this study was to determine the relationship between inhibition of IGF-I responsiveness and induction of apoptosis by vitamin D analogues in breast cancer cells. Vitamin D analogues EB1089 and CB1093 inhibited autonomous and IGF-I-stimulated growth of MCF-7 and T47D cells and autonomous growth of IGF-I-insensitive Hs578T cells. In MCF-7 cells, IGF-I alone (4 nM) protected against apoptosis mediated by serum deprivation. Co-treatment with vitamin D analogues prevented the anti-apoptotic effects of IGF-I. In T47D cells, IGF-I treatment provided only partial protection against apoptosis induced by serum deprivation and co-incubation of serum-deprived cells with 100 nM CB1093 and IGF-I abrogated this partial protection. In Hs578T cells, addition of IGF-I did not prevent apoptosis induced by serum deprivation. However, treatment with CB1093 attenuated the protective effect of the serum in these cells. Our findings suggest that vitamin D analogues inhibit IGF-I signalling pathways to promote apoptosis in breast cancer cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis*
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / pathology*
  • Calcitriol / therapeutic use*
  • Cell Communication
  • Female
  • Humans
  • Immunoblotting
  • Insulin-Like Growth Factor I / antagonists & inhibitors*
  • Receptor, IGF Type 1 / drug effects
  • Tumor Cells, Cultured / drug effects


  • Insulin-Like Growth Factor I
  • Receptor, IGF Type 1
  • Calcitriol