Biological activities of 2alpha-substituted analogues of 1alpha,25-dihydroxyvitamin D3 in transcriptional regulation and human promyelocytic leukemia (HL-60) cell proliferation and differentiation

Biol Pharm Bull. 2006 Nov;29(11):2246-50. doi: 10.1248/bpb.29.2246.

Abstract

Biological activities of 2alpha-substituted 1alpha,25-dihydroxyvitamin D3 analogues were evaluated in vitro. Their binding affinity was examined with calf thymus cytosolic vitamin D receptor (VDR) and rat plasma vitamin D-binding protein (DBP). In addition, the transcriptional activity of the analogues was measured using a rat 25-hydroxyvitamin D3-24-hydroxylase gene promoter, a human osteocalcin gene promoter, and VDR-GAL4 system. This study investigated the biological activities of 2alpha-substituted analogues in comparison with 2beta-substitued analogues at the molecular level, with regard to the structural differences of alkyl, hydroxyalkyl, hydroxyalkoxy substituents at the 2-position of 1alpha,25-dihydroxyvitamin D3.

MeSH terms

  • Animals
  • CD11b Antigen / biosynthesis
  • Calcitriol / analogs & derivatives
  • Calcitriol / metabolism
  • Calcitriol / pharmacology*
  • Cattle
  • Cell Cycle / drug effects
  • Cell Differentiation / drug effects*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Flow Cytometry
  • HL-60 Cells
  • Humans
  • Lipopolysaccharide Receptors / biosynthesis
  • Luciferases / genetics
  • Luciferases / metabolism
  • Molecular Structure
  • Osteocalcin / pharmacology
  • Protein Binding / drug effects
  • Rats
  • Receptors, Calcitriol / genetics
  • Receptors, Calcitriol / metabolism
  • Steroid Hydroxylases / genetics
  • Steroid Hydroxylases / metabolism
  • Structure-Activity Relationship
  • Transcriptional Activation / drug effects*
  • Transcriptional Activation / genetics
  • Transfection
  • Vitamin D-Binding Protein / genetics
  • Vitamin D-Binding Protein / metabolism
  • Vitamin D3 24-Hydroxylase

Substances

  • CD11b Antigen
  • Lipopolysaccharide Receptors
  • Receptors, Calcitriol
  • Vitamin D-Binding Protein
  • Osteocalcin
  • Luciferases
  • Steroid Hydroxylases
  • Vitamin D3 24-Hydroxylase
  • Calcitriol