Induction of differentiation of U-937 cells by 2-chloro-3-amino-1,4-naphthoquinone

Res Commun Mol Pathol Pharmacol. 1997 Aug;97(2):215-27.

Abstract

Naphthoquinone compounds have various pharmacological effects such as antiviral, antifungal and anticancer activities. We demonstrated the differentiation of the inducing effect of a naphthoquinone derivative, 2-chloro-3-amino-1,4-nahpthoquinone (NQCA) on the human leukemia cell line U-937. When U-937 cells were treated with NQCA for 4 days, phenotypes indicative of differentiation such as nitroblue tetrazolium (NBT)-reducing activity and phagocytosis were induced. To evaluate the route of differentiation of U-937 cells induced by NQCA, we determined naphthol AS-D chloroacetate esterase and alpha-naphthyl acetate esterase activities. Four days treatment of U-937 cells with NQCA increased alpha-naphthyl acetate esterase activity about 63.5% but naphthol AS-D chloroacetate esterase was not detected. These results indicate that NQCA caused differentiation of U-937 cells into macrophage-like cells. Since protein kinase C (PKC) and protein kinase A (PKA) have important roles in cell-differentiation and proliferation, we employed a PKC inhibitor NA-382 and a PKA inhibitor H-89 to examine the effects of each kinase on the differentiation of U-937 cells. The PKC inhibitor NA-382 decreased the effect of NQCA on U-937 cells, while the PKA inhibitor H-89 did not. Also glutathione (GSH) inhibited the effect of NQCA. It is concluded that the differentiation-inducing effect of NQCA on U-937 cells may be attributed to PKC activation followed by production of free radicals.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaloids / pharmacology
  • Cell Differentiation / drug effects*
  • Cyclic AMP-Dependent Protein Kinases / antagonists & inhibitors*
  • Enzyme Activation / drug effects
  • Enzyme Inhibitors / pharmacology
  • Glutathione / metabolism
  • Humans
  • Isoquinolines / pharmacology
  • Naphthol AS D Esterase / analysis
  • Naphthoquinones / pharmacology*
  • Nitroblue Tetrazolium
  • Phagocytosis / drug effects
  • Protein Kinase C / antagonists & inhibitors*
  • Staurosporine / analogs & derivatives
  • Sulfonamides*
  • Tumor Cells, Cultured / drug effects

Substances

  • Alkaloids
  • Enzyme Inhibitors
  • Isoquinolines
  • Naphthoquinones
  • Sulfonamides
  • N-ethoxycarbonyl-7-oxostaurosporine
  • 2-chloro-3-amino-1,4-naphthoquinone
  • Nitroblue Tetrazolium
  • Cyclic AMP-Dependent Protein Kinases
  • Protein Kinase C
  • Naphthol AS D Esterase
  • Glutathione
  • Staurosporine
  • N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide