| G-quadruplex-binding benzo[a]phenoxazines down-regulate c-KIT expression in human gastric carcinoma cells. | |
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MedLine Citation:
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PMID: 21294544 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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There is considerable interest in the structure and function of G-quadruplex nucleic acid secondary structures, their cellular functions, and their potential as therapeutic targets. G-Quadruplex sequence motifs are prevalent in gene promoter regions and it has been hypothesized that G-quadruplex structure formation is associated with the transcriptional status of the downstream gene. Using a functional cell-based assay, we have identified two novel G-quadruplex ligands that reduce the transcription of a luciferase reporter driven from the G-quadruplex-containing c-KIT promoter. We have further shown that endogenous c-KIT expression in a human gastric carcinoma cell line is also reduced on treatment with these molecules. Biophysical analysis using surface plasmon resonance has shown that these molecules preferentially bind with high affinity to one of the two G-quadruplex sequences in the c-KIT promoter over double-stranded DNA. This work highlights the utility of cell-based reporter assays to identify new G-quadruplex binding molecules that modulate transcription and identifies benzo[a]phenoxazine derivatives as potential antitumor agents. |
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Authors:
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Keith I E McLuckie; Zoë A E Waller; Deborah A Sanders; David Alves; Raphaël Rodriguez; Jyotirmayee Dash; Grahame J McKenzie; Ashok R Venkitaraman; Shankar Balasubramanian |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2011-02-04 |
Journal Detail:
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Title: Journal of the American Chemical Society Volume: 133 ISSN: 1520-5126 ISO Abbreviation: J. Am. Chem. Soc. Publication Date: 2011 Mar |
Date Detail:
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Created Date: 2011-02-24 Completed Date: 2011-06-10 Revised Date: 2013-03-28 |
Medline Journal Info:
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Nlm Unique ID: 7503056 Medline TA: J Am Chem Soc Country: United States |
Other Details:
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Languages: eng Pagination: 2658-63 Citation Subset: IM |
Affiliation:
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Department of Chemistry, University of Cambridge, Cambridge, UK. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Binding Sites Down-Regulation / drug effects* G-Quadruplexes* Gene Expression Regulation, Neoplastic / drug effects* Humans Molecular Structure Oxazines / chemistry, pharmacology* Polymerase Chain Reaction Proto-Oncogene Proteins c-kit / genetics* RNA, Messenger / genetics Stomach Neoplasms / genetics*, pathology* Surface Plasmon Resonance Tumor Cells, Cultured |
| Grant Support | |
ID/Acronym/Agency:
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A5709//Cancer Research UK; //Biotechnology and Biological Sciences Research Council; //Cancer Research UK |
| Chemical | |
Reg. No./Substance:
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0/Oxazines; 0/RNA, Messenger; EC 2.7.10.1/Proto-Oncogene Proteins c-kit |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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