Head and neck cancer radiosensitization by the novel poly(ADP-ribose) polymerase inhibitor GPI-15427

Khurram Khan, Koji Araki, Daiyou Wang, Guayan Li, Xin Li, Jie Zhang, Weizheng Xu, Randall K. Hoover, Susan Lauter, Bert O'Malley, Rena G. Lapidus, Daqing Li

Research output: Contribution to journalArticle

Abstract

Background. In this study, we tested the ability of a novel poly(adenosine diphosphate ribose) polymerase (PARP) inhibitor, 10-(4-methyl-piperazin-1- ylmethyl)-2H-7-oxa-1,2-diaza-benzo[de]-anthracen-3-one (GPI-15427), to enhance the effect of radiotherapy in a xenograft model of human head and neck squamous cell carcinoma (HNSCC). Methods. Human xenograft HNSCC tumors were established in female nude mice: animals were treated with orally administered GPI-15427 at varied doses prior to tumor irradiation. In vitro and in vivo apoptosis analyses and neutral single-cell gel electrophoresis (comet) assay were performed, with the "tail moment" calculated to evaluate DNA double-strand break damage. Results. Orally administered GPI-15427 given before radiation therapy significantly reduced tumor volume, and cells demonstrated significantly elevated mean tail moments (indicative of DNA damage) and enhanced apoptosis both in vitro and in vivo, compared with radiation-alone and control groups. Conclusions. Use of the PARP-1 inhibitor GPI-15427 induced significant sensitization to radiotherapy, representing a promising new treatment in the management of HNSCC.

Original languageEnglish (US)
Pages (from-to)381-391
Number of pages11
JournalHead and Neck
Volume32
Issue number3
DOIs
StatePublished - Mar 2010
Externally publishedYes

Keywords

  • DNA repair
  • HNSCC
  • PARP inhibition
  • Radio-sensitizing
  • Strand breaks

ASJC Scopus subject areas

  • Otorhinolaryngology

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  • Cite this

    Khan, K., Araki, K., Wang, D., Li, G., Li, X., Zhang, J., Xu, W., Hoover, R. K., Lauter, S., O'Malley, B., Lapidus, R. G., & Li, D. (2010). Head and neck cancer radiosensitization by the novel poly(ADP-ribose) polymerase inhibitor GPI-15427. Head and Neck, 32(3), 381-391. https://doi.org/10.1002/hed.21195