Bae K A, Choung S Y
Department of Hygienic Chemistry, College of Pharmacy, Kyung Hee University, Seoul, Korea.
Biol Pharm Bull. 1996 Jun;19(6):824-7. doi: 10.1248/bpb.19.824.
There are some highly cytotoxic anticancer compounds inducing differentiation of cancer cells to normal cells at below highly cytotoxic concentration. Naphthoquinone derivatives having cytotoxic effects on cancer cell were tested to learn whether they have differentiation inducing activity in human leukemia HL-60 cells or not. When HL-60 cells were treated with 2-chloro-3-amino-1,4-naphthoquinone (CANQ) for four days, differentiation-related phenotypes such as nitrobluetetrazolium (NBT)-reducing ability and phagocytosis were induced. These differentiation markers were increased by cotreatment with 1,25-dihydroxyvitamin D3 which is a well-known inducer of differentiation in HL-60 cells. To evaluate the route of differentiation induced by CANQ, we examined naphthol AS-D chloroacetate esterase and alpha-naphthylacetate esterase activities and changes in cellular size and granulation. Treatment of HL-60 cells with CANQ for four days resulted in an 82.4% increase in alpha-naphthylacetate esterase activity in spite of a 0.2% increase in naphthol AS-D chloroacetate esterase activity. The size of cells in cell mass was larger and granulation was more decreased than untreated cells. These results indicate that HL-60 cells were induced to differentiate into macrophage-like cells.
有一些高细胞毒性的抗癌化合物在低于高细胞毒性浓度时可诱导癌细胞分化为正常细胞。对具有癌细胞细胞毒性作用的萘醌衍生物进行了测试，以了解它们在人白血病HL-60细胞中是否具有诱导分化活性。当用2-氯-3-氨基-1,4-萘醌（CANQ）处理HL-60细胞四天时，诱导了与分化相关的表型，如硝基蓝四氮唑（NBT）还原能力和吞噬作用。这些分化标志物通过与1,25-二羟基维生素D3共同处理而增加，1,25-二羟基维生素D3是HL-60细胞中一种众所周知的分化诱导剂。为了评估CANQ诱导的分化途径，我们检测了萘酚AS-D氯乙酸酯酶和α-萘乙酸酯酶活性以及细胞大小和颗粒化的变化。用CANQ处理HL-60细胞四天后，α-萘乙酸酯酶活性增加了82.4%，尽管萘酚AS-D氯乙酸酯酶活性仅增加了0.2%。细胞团中细胞的大小比未处理的细胞更大，颗粒化程度更低。这些结果表明HL-60细胞被诱导分化为巨噬细胞样细胞。
