Vitamin D3 analogs and their 24-oxo metabolites equally inhibit clonal proliferation of a variety of cancer cells but have differing molecular effects

J Cell Biochem. 1997 Sep 1;66(3):413-25.


The seco-steroid hormone, 1 alpha, 25 dihydroxyvitamin D3 (1 alpha,25(OH)2D3) binds to a specific nuclear receptor that acts as a ligand-inducible transcription factor. The resulting genomic effects include partial arrest in G0/G1 of the cell cycle and induction of differentiation; these effects have been observed in various types of cancer. Recently, we produced enzymatically the natural 24-oxo metabolites of 1 alpha,25(OH)2D3 and two of its potent synthetic analogs (1 alpha,25-(OH)2-16-ene-D3 and 1 alpha,25-(OH)2-20-epi-D3) using a rat kidney perfusion system. We have found that the 24-oxo metabolites of both 1 alpha,25(OH)2D3 and its analogs have either the same or greater antiproliferative activity against various cancer cells as their parental compounds. Notably, two cell lines (DU-145 (prostate cancer) and MDA-MB-436 [breast cancer]) that were extremely resistant to the antiproliferative effects of vitamin D3 analogs displayed greater sensitivity towards the 24-oxo metabolite of the vitamin D3 analog. Similarly, the 24-oxo metabolites had the capacity to induce differentiation and apoptosis and to diminish the proportion of cells in S phase. Most interestingly, while the analog 1 alpha,25(OH)2-20-epi-D3 induced expression of BRCA1 in MCF-7 breast cancer cells; its 24-oxo metabolite dramatically suppressed BRAC1 expression. Thus, we have shown for the first time that the various biological activities produced by the hormone 1 alpha,25(OH)2D3 and some of its analogs may represent a combination of actions by the hormone 1 alpha,25(OH)2D3 and its natural 24-oxo metabolites.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Apoptosis / drug effects
  • BRCA1 Protein / drug effects
  • BRCA1 Protein / genetics
  • BRCA1 Protein / metabolism
  • Breast Neoplasms / drug therapy
  • Cadherins / drug effects
  • Cadherins / genetics
  • Cadherins / metabolism
  • Calcitriol / analogs & derivatives
  • Calcitriol / metabolism
  • Calcitriol / pharmacology
  • Cell Cycle / drug effects
  • Cell Cycle Proteins*
  • Cell Division / drug effects
  • Cholecalciferol / analogs & derivatives*
  • Cholecalciferol / metabolism
  • Cholecalciferol / pharmacology*
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclin-Dependent Kinase Inhibitor p27
  • Cyclins / drug effects
  • Cyclins / genetics
  • Cyclins / metabolism
  • HL-60 Cells / drug effects
  • Humans
  • Male
  • Microtubule-Associated Proteins / drug effects
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism
  • Neoplasms / drug therapy*
  • Prostatic Neoplasms / drug therapy
  • Proto-Oncogene Proteins / drug effects
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-bcl-2*
  • Tumor Cells, Cultured
  • Tumor Suppressor Proteins*
  • bcl-2-Associated X Protein


  • BRCA1 Protein
  • CDKN1A protein, human
  • Cadherins
  • Cell Cycle Proteins
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins
  • Microtubule-Associated Proteins
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Tumor Suppressor Proteins
  • bcl-2-Associated X Protein
  • 1,25-dihydroxy-16-ene-vitamin D3
  • Cyclin-Dependent Kinase Inhibitor p27
  • Cholecalciferol
  • 1,25-dihydroxy-24-oxo-vitamin D3
  • Calcitriol