Smenospongine, a spongean sesquiterpene aminoquinone, induces erythroid differentiation in K562 cells
Smenospongine, a spongean sesquiterpene aminoquinone, induces erythroid differentiation in K562 cells
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DOI：
10.1097/00001813-200404000-00009
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发表时间：
2004-04-01
影响因子：
2.3
通讯作者：
Kobayashi, M
中科院分区：
文献类型：
--
作者：
Aoki, S;Kong, D;Kobayashi, M
研究了苦参碱对K562慢性粒细胞白血病(CML)细胞的诱导分化作用。在3-15微米的浓度下，司马松平能增加K562细胞的血红蛋白产量。此外，用FITC标记的血糖素A抗体对苦参碱处理的K562细胞进行的流式细胞术分析显示，血糖素A的表达增加，这是红系分化的标志。细胞周期分析显示，司米诺松处理K562细胞24 h后，细胞周期停滞于G(1)期，Western blotting检测了CIP/KIP家族细胞周期蛋白依赖性激酶抑制物对K562细胞p21表达的影响，发现p21在K562细胞分化中起重要作用。此外，还发现司米松碱还抑制BCR-Abl酪氨酸激酶底物Crk1的磷酸化，Crk1是CML的致病蛋白。综上所述，我们的研究表明司米诺松可诱导K562细胞分化为红系细胞，并使细胞周期停滞于G(1)期，其机制可能与上调p21的表达有关。(C)2004年，里平科特·威廉姆斯·威尔金斯。
The differentiation of K562 chronic myelogenous leukemia (CML) cells by smenospongine, which is a sesquiterpene aminoquinone isolated from a marine sponge, was examined. Smenospongine increased hemoglobin production in K562 cells at concentrations of 3-15 muM. In addition, flow cytometric analysis of smenospongine-treated K562 cells with FITC-labeled glycophorin A antibody showed an increase of glycophorin A expression, a marker for erythroid differentiation. Cell-cycle analysis showed G(1) arrest in K562 cells after treatment with smenospongine for 24 h. The effect on expression of CIP/KIP family cyclin-dependent kinase inhibitors was investigated by Western blotting analysis and the result showed increased expression of p21, which is known to play an important role in differentiation. Furthermore, smenospongine was also found to inhibit the phosphorylation of Crkl, a substrate of Bcr-Abl tyrosine kinase, which is known as a causative protein of CML. In conclusion, our investigation indicated that smenospongine induced the differentiation of K562 cells into erythroblasts; along with cell-cycle arrest at G(1) phase and the mechanism might be attributed to the increased expression of p21. (C) 2004 Lippincott Williams Wilkins.