Inhibition of Plk1 and Cyclin B1 expression results in panobinostat-induced G2 delay and mitotic defects.

Michael B. Prystowsky, Katherine Feeney, Nicole Kawachi, Cristina Montagna, Michelle Willmott, Christopher Wasson, Maciej Antkowiak, Olivier Loudig, Joanna Parish

Research output: Contribution to journalArticle

7 Citations (Scopus)

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 G2/M and an associated decrease in expression of particular genes required for passage through G2 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 G2 delay and mitotic defects. A loss of G2-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.

Original languageEnglish (US)
Pages (from-to)2640
Number of pages1
JournalScientific Reports
Volume3
StatePublished - 2013

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Cyclin B1
Mitosis
Cell Line
Histone Deacetylase Inhibitors
Cell Cycle Checkpoints
panobinostat
Cell Cycle
Gene Expression
Growth
Genes
Carcinoma, squamous cell of head and neck

ASJC Scopus subject areas

  • General

Cite this

Inhibition of Plk1 and Cyclin B1 expression results in panobinostat-induced G2 delay and mitotic defects. / Prystowsky, Michael B.; Feeney, Katherine; Kawachi, Nicole; Montagna, Cristina; Willmott, Michelle; Wasson, Christopher; Antkowiak, Maciej; Loudig, Olivier; Parish, Joanna.

In: Scientific Reports, Vol. 3, 2013, p. 2640.

Research output: Contribution to journalArticle

Prystowsky, MB, 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 G2 delay and mitotic defects.', Scientific Reports, vol. 3, pp. 2640.
Prystowsky, Michael B. ; Feeney, Katherine ; Kawachi, Nicole ; Montagna, Cristina ; Willmott, Michelle ; Wasson, Christopher ; Antkowiak, Maciej ; Loudig, Olivier ; Parish, Joanna. / Inhibition of Plk1 and Cyclin B1 expression results in panobinostat-induced G2 delay and mitotic defects. In: Scientific Reports. 2013 ; Vol. 3. pp. 2640.
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AU - Montagna, Cristina

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AU - Wasson, Christopher

AU - Antkowiak, Maciej

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