Development of a novel cell-based assay system EPISSAY for screening epigenetic drugs and liposome formulated decitabine

Lim, Sue Ping, Kumar, Raman, Akkamsetty, Yamini, Wang, Wen, Ho, Kristen, Neilsen, Paul M., Walther, Diego J., Suetani, Rachel J., Prestidge, Clive and Callen, David F. (2013) Development of a novel cell-based assay system EPISSAY for screening epigenetic drugs and liposome formulated decitabine. BMC Cancer, 13 113.1-113.11. doi:10.1186/1471-2407-13-113


Author Lim, Sue Ping
Kumar, Raman
Akkamsetty, Yamini
Wang, Wen
Ho, Kristen
Neilsen, Paul M.
Walther, Diego J.
Suetani, Rachel J.
Prestidge, Clive
Callen, David F.
Title Development of a novel cell-based assay system EPISSAY for screening epigenetic drugs and liposome formulated decitabine
Journal name BMC Cancer   Check publisher's open access policy
ISSN 1471-2407
Publication date 2013-03-13
Sub-type Article (original research)
DOI 10.1186/1471-2407-13-113
Open Access Status DOI
Volume 13
Start page 113.1
End page 113.11
Total pages 11
Place of publication London, United Kingdom
Publisher BioMed Central
Language eng
Formatted 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.
Keyword CB1954
Cell-based assay system
Decitabine
Liposomes
Nanotechnology
Nitroreductase
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Queensland Brain Institute Publications
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 1 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 3 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Mon, 30 Nov 2015, 09:21:19 EST by Rachel Suetani on behalf of Queensland Brain Institute