Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/79522
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Type: | Journal article |
Title: | Development of a novel cell-based assay system EPISSAY for screening epigenetic drugs and liposome formulated decitabine |
Author: | Lim, S. Kumar, R. Akkamsetty, Y. Wang, W. Ho, K. Neilsen, P. Walther, D. Suetani, R. Prestidge, C. Callen, D. |
Citation: | BMC Cancer, 2013; 13(113):1-11 |
Publisher: | BioMed Central Ltd. |
Issue Date: | 2013 |
ISSN: | 1471-2407 1471-2407 |
Statement of Responsibility: | Sue Ping Lim, Raman Kumar, Yamini Akkamsetty, Wen Wang, Kristen Ho, Paul M. Neilsen, Diego J. Walther, Rachel J. Suetani, Clive Prestidge and David F. Callen |
Abstract: | BACKGROUND: Despite the potential of improving the delivery of epigenetic drugs, the subsequent assessment of changes in their epigenetic activity is largely dependent on the availability of a suitable and rapid screening bioassay. Here, we describe a cell-based assay system for screening gene reactivation. METHODS: A cell-based assay system (EPISSAY) was designed based on a silenced triple-mutated bacterial nitroreductase TMnfsB fused with Red-Fluorescent Protein (RFP) expressed in the non-malignant human breast cell line MCF10A. EPISSAY was validated using the target gene TXNIP, which has previously been shown to respond to epigenetic drugs. The potency of a epigenetic drug model, decitabine, formulated with PEGylated liposomes was also validated using this assay system. RESULTS: Following treatment with DNA methyltransferase (DNMT) and histone deacetylase (HDAC) inhibitors such as decitabine and vorinostat, increases in RFP expression were observed, indicating expression of RFP-TMnfsB. The EPISSAY system was then used to test the potency of decitabine, before and after PEGylated liposomal encapsulation. We observed a 50% higher potency of decitabine when encapsulated in PEGylated liposomes, which is likely to be due to its protection from rapid degradation. CONCLUSIONS: The EPISSAY bioassay system provides a novel and rapid system to compare the efficiencies of existing and newly formulated drugs that reactivate gene expression. |
Keywords: | Cell-based assay system decitabine liposomes nanotechnology CB1954 nitroreductase |
Description: | Extent: 11 p. |
Rights: | © 2013 Lim et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the CreativeCommons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, andreproduction in any medium, provided the original work is properly cited. |
DOI: | 10.1186/1471-2407-13-113 |
Published version: | http://dx.doi.org/10.1186/1471-2407-13-113 |
Appears in Collections: | Aurora harvest 7 Medicine publications |
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hdl_79522.pdf | Published version | 604.37 kB | Adobe PDF | View/Open |
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