A novel DNA polymerase inhibitor and a potent apoptosis inducer: 2-mono-O-acyl-3-O-(alpha-D-sulfoquinovosyl)-glyceride with stearic acid.

A novel DNA polymerase inhibitor and a potent apoptosis inducer: 2-mono-O-acyl-3-O-(alpha-D-sulfoquinovosyl)-glyceride with stearic acid.
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一种新型 DNA 聚合酶抑制剂和有效的细胞凋亡诱导剂:2-单-O-酰基-3-O-(α-D-磺基喹诺酰基)-甘油酯与硬脂酸。

DOI:
10.1016/s1570-9639(02)00521-6
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发表时间:
2003
期刊:
Biochimica et biophysica acta
影响因子:
--
通讯作者:
Y. Mizushina
Y. Mizushina
中科院分区:
--
文献类型:
--
作者:
C. Murakami;T. Yamazaki;S. Hanashima;Shunya Takahashi;M. Takemura;S. Yoshida;K. Ohta;H. Yoshida;F. Sugawara;K. Sakaguchi;Y. Mizushina

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磺基喹诺酮基二酰甘油中的磺基糖脂,包括立体异构体,是α和β的有效抑制剂。然而,由于含有两种硬脂酸的α构型(α-SQDG-C18)几乎不能穿透细胞,所以它没有细胞毒性作用。我们尝试并成功地以α-SQDG-C18为原料,经胰酶水解法合成了含硬脂酸的磺基喹诺酮单酰甘油(α-SQMG-C18)。α-SQMG-C18抑制DNA聚合酶活性,对肿瘤细胞的生长有明显的抑制作用。α-SQMG-C18使细胞周期停滞于G1期,并诱导严重的细胞凋亡。α-SqMG-C18通过P53依赖的细胞凋亡途径诱导细胞死亡,与P53和细胞周期蛋白E表达增加有关。
Sulfo-glycolipids in the class of sulfoquinovosyl diacylglycerol (SQDG) including the stereoisomers are potent inhibitors of DNA polymerase α and β. However, since the α-configuration of SQDG with two stearic acids (α-SQDG-C18) can hardly penetrate cells, it has no cytotoxic effect. We tried and succeeded in making a permeable form, sulfoquinovosyl monoacylglycerol with a stearic acid (α-SQMG-C18) from α-SQDG-C18by hydrolysis with a pancreatic lipase. α-SQMG-C18inhibited DNA polymerase activity and was found to be a potent inhibitor of the growth of NUGC-3 cancer cells. α-SQMG-C18arrested the cell cycle at the G1 phase, and subsequently induced severe apoptosis. The arrest was correlated with an increased expression of p53 and cyclin E, indicating that α-SQMG-C18induced cell death through a p53-dependent apoptotic pathway.
DOI: 10.1126/science.1329201
发表时间: 1992-09-25
期刊: SCIENCE
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