Folate-functionalized human serum albumin carrier for anticancer copper(II) complexes derived from natural plumbagin
Folate-functionalized human serum albumin carrier for anticancer copper(II) complexes derived from natural plumbagin
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叶酸功能化人血清白蛋白载体，用于源自天然白花丹素的抗癌铜（II）络合物
DOI：
10.1016/j.jinorgbio.2015.09.004
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发表时间：
2015-12-01
影响因子：
3.9
通讯作者：
Liang, Hong
中科院分区：
文献类型：
--
作者：
Gou, Yi;Zhang, Zhan;Liang, Hong
叶酸功能化人血清白蛋白载体（FA-HSA）有望提高抗癌药物的靶向性和效率。为开发FA-HSA载体用于金属抗癌药物的载体，研究了白花丹醌铜（II）配合物FA-HSA载体的抗癌性能和机理。荧光光谱和分子对接表明，Cu（II）配合物与HSA的IIA亚结构域结合。与单独的Cu（II）配合物相比，FA-HSA-金属药物配合物在体外对FA阳性癌细胞（HeLa）的细胞毒作用增强，但在正常细胞中的细胞毒作用不增强，这是由于FA-HSA-金属药物配合物在癌细胞中有一定程度的选择性蓄积; FA-HSA-金属药物复合物对HeLa细胞G2/M期的细胞周期阻滞能力较强，下调细胞周期蛋白依赖性激酶1（CDK 1）和细胞周期蛋白B1的表达。FA-HSA-metallodrug复合物通过内源性活性氧介导的线粒体途径促进HeLa细胞凋亡，并伴有Bcl-2家族蛋白的调节。(C)© 2015 Elsevier Inc版权所有。
The folate (FA)-functionalized human serum albumin (HSA) carrier (FA-HSA) is promising for improving the target and efficiency of anticancer drugs. To develop FA-HSA carrier for metal anticancer drugs, we investigated anticancer properties and mechanism of FA-HSA carrier for Cu(II) complexes derived from plumbagin. The fluorescence spectroscopy and molecular docking revealed that Cu(II) complexes bind to IIA subdomain of HSA. Compared with Cu(II) complex alone, FA-HSA-metallodrug complex enhances cytotoxicity to FA-positive cancer cells (HeLa) but do not raise cytotoxicity levels in normal cells in vitro through selectively accumulating in cancer cells to some extent; FA-HSA-metallodrug complex has a stronger capacity for cell cycle arrest in the G2/M phase of HeLa cells, and down-regulating the expression of cydin-dependent kinase 1 (CDK1) and cyclin B1. Moreover, FA-HSA-metallodrug complex promotes HeLa cells apoptosis through intrinsic reactive oxygen species (ROS) mediated mitochondrial pathway, accompanied by the regulation of Bcl-2 family proteins. (C) 2015 Elsevier Inc All rights reserved.