Please use this identifier to cite or link to this item: http://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.
RMID: 0020128750
DOI: 10.1186/1471-2407-13-113
Appears in Collections:Medicine publications

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