Induction of differentiation of U-937 cells by 2-chloro-3-amino-1,4-naphthoquinone.
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.
Kwon
H
H
Department of Hygienic Chemistry, College of Pharmacy, Kyoung Hee University, Seoul, Korea.
Choung
S Y
SY
D000470:Alkaloids / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors*; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology; D009283:Naphthol AS D Esterase / Q000032:analysis; D009285:Naphthoquinones / Q000494:pharmacology*; D009580:Nitroblue Tetrazolium; D010587:Phagocytosis / Q000187:drug effects; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D019311:Staurosporine / Q000031:analogs & derivatives; D013449:Sulfonamides; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000470:Alkaloids; D004791:Enzyme Inhibitors; D007546:Isoquinolines; D009285:Naphthoquinones; D013449:Sulfonamides; C075317:N-ethoxycarbonyl-7-oxostaurosporine; C102441:2-chloro-3-amino-1,4-naphthoquinone; D009580:Nitroblue Tetrazolium; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D009283:Naphthol AS D Esterase; D005978:Glutathione; D019311:Staurosporine; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide