Induction of apoptosis by vitamin D3 analogue EB1089 in NCI-H929 myeloma cells via activation of caspase 3 and p38 MAP kinase

Br J Haematol. 2000 Jun;109(3):576-83. doi: 10.1046/j.1365-2141.2000.02046.x.


EB1089, a novel 1,25-dihydroxyvitamin D3 analogue, has been known to have potent antiproliferative properties in a variety of malignant cells both in vitro and in vivo. In the present study, we analysed the effect of EB1089 on NCI-H929 human myeloma cells. EB1089 inhibited cell growth of NCI-H929 and efficiently induced the G1 phase arrest of the cell cycle in a dose-dependent manner. We could also detect apoptosis in NCI-H929 cells exposed to EB1089 (1 x 10-7 M for 72 h) using the sub-G1 group of the cell cycle by FACS and annexin V binding assays. Induction of apoptosis by EB1089 was associated with down-regulation of the Bcl-2 protein without change of the Bax protein. Regarding caspase activity, which plays a crucial role in apoptosis, EB1089-treated NCI-H929 cells revealed an increased activity of caspase 3 protease accompanied by degradation of the PARP protein in a dose- and time-dependent manner. In addition, EB1089 caused the down-regulation of p44 extracellular signal-related kinase (ERK) activity and up-regulation of the p38 kinase activity during apoptosis of NCI-H929 cells. These results suggest that EB1089 inhibits growth of NCI-H929 cells via G1 cell cycle arrest as well as apoptosis by activating p38 kinase and suppressing ERK activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / therapeutic use*
  • Apoptosis / drug effects
  • Blotting, Western
  • Calcitriol / analogs & derivatives*
  • Calcitriol / therapeutic use
  • Caspase 3
  • Caspases / metabolism*
  • Cholecalciferol / analogs & derivatives*
  • Enzyme Activation / drug effects
  • Humans
  • Mitogen-Activated Protein Kinases / metabolism*
  • Multiple Myeloma / drug therapy*
  • Multiple Myeloma / enzymology
  • Tumor Cells, Cultured
  • p38 Mitogen-Activated Protein Kinases


  • Antineoplastic Agents
  • Cholecalciferol
  • Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases
  • CASP3 protein, human
  • Caspase 3
  • Caspases
  • Calcitriol
  • seocalcitol