Vitamin D3 analogue KH1060 combined with TPA synergistically induces mature macrophages in human myeloblastic leukemia ML-1 cells

Anticancer Res. Mar-Apr 1999;19(2A):1069-76.

Abstract

A human myeloblastic leukemia cell line, ML-1, was induced to differentiate along the monocytic lineage following exposure to a 1,25-dihydroxyvitamin D3 analogue, 20-epi-22-oxa-24a,26a,27a-tri-homo-1,25-dihydroxyvitam in D3 (KH1060) or 12-O-tetradecanoylphorbol-13-acetate (TPA). The combination of KH1060 and TPA synergistically induced differentiation of ML-1 cells into mature macrophages with multinuclei. Maturation was also observed in other differentiation characteristics such as phagocytic activity, a-naphthyl acetate esterase activity, and expression of surface antigen CD14. Differentiated ML-1 cells showed attenuation of telomerase activity and cessation of proliferating activity based on evaluation of the expression of genes related to cell growth potential. Remarkable synergism was observed in TNF production. Treatment with TPA prior to KH1060 resulted in only slight production of TNF; however, treatment with KH1060 preceding TPA induced a substantial amount of TNF.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Calcitriol / analogs & derivatives*
  • Calcitriol / pharmacology
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins / genetics
  • Dose-Response Relationship, Drug
  • Drug Synergism
  • Genes, myc
  • Humans
  • Leukemia, Myeloid, Acute / pathology*
  • Macrophages / drug effects*
  • Telomerase / metabolism
  • Tetradecanoylphorbol Acetate / pharmacology*
  • Tumor Cells, Cultured
  • Tumor Necrosis Factor-alpha / biosynthesis

Substances

  • CDKN1A protein, human
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins
  • Tumor Necrosis Factor-alpha
  • KH 1060
  • Telomerase
  • Calcitriol
  • Tetradecanoylphorbol Acetate