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

Research communications in molecular pathology and pharmacology (1997-08-01)
H Kwon, S Y Choung

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.

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Quinoclamine, PESTANAL®, analytical standard

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