title: PLGA-Loaded Gold-Nanoparticles Precipitated with Quercetin Downregulate HDAC-Akt Activities Controlling Proliferation and Activate p53-ROS Crosstalk to Induce Apoptosis in Hepatocarcinoma Cells.
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 cell 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.
authors.affiliation: Department of Pharmacology, College of Medicine, Institute of Natural Medicine, Hallym University, Chuncheon 200-702, Korea.|Cytogenetics and Molecular Biology Laboratory, Department of Zoology, University of Kalyani, Kalyani 741235, India.
authors.forename: Kausik
authors.initials: K
authors.lastname: Bishayee
authors.affiliation: Cytogenetics and Molecular Biology Laboratory, Department of Zoology, University of Kalyani, Kalyani 741235, India.
authors.forename: Anisur Rahman
authors.initials: AR
authors.lastname: Khuda-Bukhsh
authors.affiliation: Department of Pharmacology, College of Medicine, Institute of Natural Medicine, Hallym University, Chuncheon 200-702, Korea.
authors.forename: Sung-Oh
authors.initials: SO
authors.lastname: Huh
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D006046:Gold / Q000008:administration & dosage* / Q000737:chemistry; D006367:HeLa Cells; D056945:Hep G2 Cells; D056284:Histone Deacetylase 1 / Q000378:metabolism; D056464:Histone Deacetylase 2 / Q000378:metabolism; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D019344:Lactic Acid / Q000008:administration & dosage* / Q000737:chemistry; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D053768:Metal Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D011100:Polyglycolic Acid / Q000008:administration & dosage* / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011794:Quercetin / Q000008:administration & dosage* / Q000737:chemistry; D017382:Reactive Oxygen Species / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D006046:Gold; D011794:Quercetin; C110550:HDAC1 protein, human; C533423:HDAC2 protein, human; D056284:Histone Deacetylase 1; D056464:Histone Deacetylase 2; D006655:Histone Deacetylases
keywords: apoptosis; gold-nanoparticles; histone deacetylation; p53-ROS crosstalk; quercetin