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

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

Research output: Contribution to journalArticlepeer-review

11 Scopus citations


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 p21Waf1/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)
Article number2640
JournalScientific reports
StatePublished - Sep 12 2013

ASJC Scopus subject areas

  • General


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