PLGA-Loaded Gold-Nanoparticles Precipitated with Quercetin Downregulate HDAC-Akt Activities Controlling Proliferation and Activate p53-ROS Crosstalk to Induce Apoptosis in Hepatocarcinoma Cells.
PLGA-Loaded Gold-Nanoparticles Precipitated with Quercetin Downregulate HDAC-Akt Activities Controlling Proliferation and Activate p53-ROS Crosstalk to Induce Apoptosis in Hepatocarcinoma Cells.
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DOI：
10.14348/molcells.2015.2339
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发表时间：
2015-06
影响因子：
3.8
通讯作者：
Huh SO
中科院分区：
文献类型：
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作者：
Bishayee K;Khuda-Bukhsh AR;Huh SO
药物控释仍然是最方便的药物输送方式。在这项研究中，我们沉淀金纳米粒子与槲皮素。将金-槲皮素负载到聚（DL-丙交酯-乙交酯）纳米粒（NQ）中，并通过对HepG 2肝癌细胞的生物学活性测试，获得了NQ的缓释特性。圆二色谱法测定表明，NQ能有效地引起DNA的构象变化，并调节与表观遗传修饰和细胞周期调控有关的不同蛋白质。采用流式细胞仪检测细胞线粒体膜电位（MMP）、活性氧（ROS）、细胞周期、凋亡、DNA损伤和caspase 3活性，免疫印迹法检测不同抗凋亡和促凋亡信号以及表观遗传信号的表达谱。细胞毒性试验表明，与正常细胞相比，NQ优先杀死癌细胞。NQ与HepG 2细胞DNA相互作用，减少组蛋白去乙酰化酶，从而控制细胞增殖，并将细胞周期阻滞在亚G期。细胞周期相关蛋白如p21 WAF、cdk 1和pAkt的活性受到调节。NQ通过激活p53-ROS串扰诱导HepG 2细胞凋亡，并诱导表观遗传修饰，导致增殖抑制和细胞周期停滞。
Controlled release of medications remains the most convenient way to deliver drugs. In this study, we precipitated gold nanoparticles with quercetin. We loaded gold-quercetin into poly(DL-lactide-co-glycolide) nanoparticles (NQ) and tested the biological activity of NQ on HepG2 hepatocarcinoma cells to acquire the sustained release property. We determined by circular dichroism spectroscopy that NQ effectively caused conformational changes in DNA and modulated different proteins related to epigenetic modifications and c ell cycle control. The mitochondrial membrane potential (MMP), reactive oxygen species (ROS), cell cycle, apoptosis, DNA damage, and caspase 3 activity were analyzed by flow cytometry, and the expression profiles of different anti- and pro-apoptotic as well as epigenetic signals were studied by immunoblotting. A cytotoxicity assay indicated that NQ preferentially killed cancer cells, compared to normal cells. NQ interacted with HepG2 cell DNA and reduced histone deacetylases to control cell proliferation and arrest the cell cycle at the sub-G stage. Activities of cell cycle-related proteins, such as p21WAF, cdk1, and pAkt, were modulated. NQ induced apoptosis in HepG2 cells by activating p53-ROS crosstalk and induces epigenetic modifications leading to inhibited proliferation and cell cycle arrest.