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http://dx.doi.org/10.14348/molcells.2015.2339

PLGA-Loaded Gold-Nanoparticles Precipitated with Quercetin Downregulate HDAC-Akt Activities Controlling Proliferation and Activate p53-ROS Crosstalk to Induce Apoptosis in Hepatocarcinoma Cells  

Bishayee, Kausik (Department of Pharmacology, College of Medicine, Institute of Natural Medicine, Hallym University)
Khuda-Bukhsh, Anisur Rahman (Cytogenetics and Molecular Biology Laboratory, Department of Zoology, University of Kalyani)
Huh, Sung-Oh (Department of Pharmacology, College of Medicine, Institute of Natural Medicine, Hallym University)
Publication Information
Molecules and Cells / v.38, no.6, 2015 , pp. 518-527 More about this Journal
Abstract
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 $p21^{WAF}$, 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.
Keywords
apoptosis; gold-nanoparticles; histone deacetylation; p53-ROS crosstalk; quercetin;
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