Mechanism of antimitogenic action of vitamin D in human colon carcinoma cells: relevance for suppression of epidermal growth factor-stimulated cell growth

Oncol Res. 1999;11(2):77-84.


Because the efficacy of 1alpha,25-dihydroxyvitamin D3 [1alpha,25-(OH)2D3] in treatment of colon cancer might critically depend on its ability to specifically counteract epidermal growth factor (EGF)-stimulated tumor cell growth, we utilized human colon adenocarcinoma-derived cells in primary culture as well as the Caco-2 cell line to elucidate possible sites of interaction of 1alpha,25-(OH)2D3 with signaling from EGF receptor activation. In both types of colon cancer cells investigated, 10(-8) M 1alpha,25-(OH)2D3 reduced basal cell proliferation by about 50%, and prevented any rise in proliferation when colon cancer cells were treated with 25 ng/ml EGF: this can be explained by a marked inhibitory effect of 1alpha,25-(OH)2D3 on EGFR mRNA and protein expression. The steroid hormone also seemingly promotes EGF-induced internalization of apical and basolateral membrane EGFR. In addition, 1alpha,25-(OH)2D3 significantly reduced basal and EGF-stimulated expression of cyclin D1 at the mRNA and protein level in primary cultures as well as in the Caco-2 cell line. The ability of 1alpha,25-(OH)2D3 to interfere with a key event in cell cycle control and thereby to block mitogenic signaling from EGF could be seen as advantageous for the potential use of vitamin D compounds in colon cancer therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Caco-2 Cells / drug effects
  • Calcitriol / pharmacology*
  • Calcium Channel Agonists / pharmacology
  • Cell Division / drug effects
  • Colonic Neoplasms / drug therapy*
  • Cyclin D1 / drug effects*
  • Cyclin D1 / metabolism
  • Epidermal Growth Factor / metabolism
  • Epidermal Growth Factor / pharmacology*
  • ErbB Receptors / drug effects*
  • ErbB Receptors / metabolism
  • Humans
  • Tumor Cells, Cultured / drug effects


  • Calcium Channel Agonists
  • Cyclin D1
  • Epidermal Growth Factor
  • ErbB Receptors
  • Calcitriol