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

Research output: Contribution to journalArticle

Authors

  • Michael Prystowsky
  • Nicole Kawachi
  • Cristina Montagna
  • Michelle Willmott
  • Christopher Wasson
  • Maciej Antkowiak
  • Olivier Loudig

Colleges, School and Institutes

External organisations

  • ALBERT EINSTEIN COLLEGE OF MEDICINE
  • University of Leeds
  • Univ St Andrews

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 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.

Details

Original languageEnglish
Article number2640
JournalScientific Reports
Volume3
Early online date12 Sep 2013
Publication statusPublished - 12 Sep 2013

Keywords

  • Cancer therapy, Oral cancer, Mitosis, Cell growth