The effect of 1,25-dihydroxyvitamin D3 on lymphoma cell lines and expression of vitamin D receptor in lymphoma

Br J Cancer. 1993 Oct;68(4):668-72. doi: 10.1038/bjc.1993.406.

Abstract

1,25(OH)2D3 promotes differentiation and has an antiproliferative effect in a variety of cell lines derived from the immunohaematopoetic system. alpha-Calcidol which is metabolised to 1,25(OH)2D3 has been shown to produce tumour regression in follicular low grade non-Hodgkin's lymphoma (NHL) and the dose limiting toxicity is hypercalcaemia. The cellular action of 1,25(OH)2D3 is mediated by binding to an intracellular protein, the vitamin D receptor (VDR). We have evaluated the activity of 1,25(OH)2D3 and its non-calcaemogenic analogue MC903 in the SU-DHL4 and SU-DUL5 B cell lines which carry the 14;18 translocation characteristic of follicular NHL, and also the expression of the VDR in a range of B cell NHLs. Both agents induced differentiation and had an antiproliferative effect on the SU-DHL4 and SU-DUL5 cell lines. However this occurred at a relatively high concentration (10(-7) M) which exceeds the physiological concentration of 1,25(OH)2D3 by approximately 10(3)-10(4)-fold. Expression of the VDR was low in each cell line and in the low grade lymphoma tumour samples. To account for the observed clinical response to 1 alpha OHD3 (alpha-calcidol) in follicular NHL a network is suggested whereby 1,25(OH)2D3 modulates the activity of CD4+T cells which have previously been shown to promote follicle centre cell proliferation. Vitamin D3 analogues may enable serum levels to be achieved which produce a direct action on follicular lymphoma cells without disturbing calcium metabolism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biopsy
  • Calcitriol / analogs & derivatives
  • Calcitriol / metabolism
  • Calcitriol / pharmacology*
  • Cell Differentiation / drug effects
  • Cell Division / drug effects
  • Drug Screening Assays, Antitumor
  • Lymph Nodes / metabolism
  • Lymph Nodes / pathology
  • Lymphoma, B-Cell / metabolism
  • Lymphoma, B-Cell / pathology*
  • Receptors, Calcitriol / drug effects
  • Receptors, Calcitriol / metabolism*
  • Tumor Cells, Cultured

Substances

  • Receptors, Calcitriol
  • calcipotriene
  • Calcitriol