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Inhibition of Plk1 and Cyclin B1 expression results in panobinostat-induced G(2) delay and mitotic defects

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Antkowiak_2013_SR_Inhibition.pdf (1.644Mb)
Date
12/09/2013
Author
Prystowsky, Michael
Feeney, Katherine
Kawachi, Nicole
Montagna, Cristina
Willmott, Michelle
Wasson, Christopher
Antkowiak, Maciej
Loudig, Olivier
Parish, Joanna
Keywords
Histone deacetylase inhibitor
Carcinoma-cell lines
Gene-expression
Cancer cells
In-vitro
LBH589
Apoptosis
Polo
Head
P53
R Medicine
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Abstract
The development of clinically useful histone deacetylase inhibitors has expanded greatly. In a preclinical study, we showed that panobinostat (LBH589) inhibits cell cycle progression of human head and neck squamous cell carcinoma (HNSCC) cell lines at G(2)/M and an associated decrease in expression of particular genes required for passage through G(2) and mitosis. In this study we sought to analyse the mechanistic underpinnings of panobinostat-induced growth arrest. HNSCC cell lines were synchronised and progression through mitosis monitored. We demonstrate that panobinostat causes a marked G(2) delay and mitotic defects. A loss of G(2)-specific Plk1 and Cyclin B1 expression and co-incident increase in p21(Waf1/Cip1) expression is also shown. Furthermore, we show a significant loss of E2F1 recruitment to the promoters of these genes in response to panobinostat treatment. These data provide mechanistic evidence of panobinostat-induced cell cycle arrest and highlight its potential as a chemotherapeutic agent for HNSCC.
Citation
Prystowsky , M , Feeney , K , Kawachi , N , Montagna , C , Willmott , M , Wasson , C , Antkowiak , M , Loudig , O & Parish , J 2013 , ' Inhibition of Plk1 and Cyclin B1 expression results in panobinostat-induced G(2) delay and mitotic defects ' , Scientific Reports , vol. 3 , e2640 . https://doi.org/10.1038/srep02640
Publication
Scientific Reports
Status
Peer reviewed
DOI
https://doi.org/10.1038/srep02640
ISSN
2045-2322
Type
Journal article
Rights
© 2013 The authors. This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/
Description
Work by JP is funded by a Royal Society University Research Fellowship award. Experiments carried out by MBP were supported by the Department of Pathology, Albert Einstein College of Medicine / Montefiore Medical Center.
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  • University of St Andrews Research
URI
http://hdl.handle.net/10023/5013

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