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

Head Neck. 2010 Mar;32(3):381-91. doi: 10.1002/hed.21195.


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.

MeSH terms

  • Administration, Oral
  • Animals
  • Apoptosis / drug effects
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / radiotherapy*
  • Comet Assay
  • Female
  • Head and Neck Neoplasms / metabolism
  • Head and Neck Neoplasms / pathology
  • Head and Neck Neoplasms / radiotherapy*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Organic Chemicals / administration & dosage
  • Organic Chemicals / pharmacokinetics
  • Organic Chemicals / therapeutic use*
  • Poly(ADP-ribose) Polymerase Inhibitors*
  • Radiation-Sensitizing Agents / administration & dosage
  • Radiation-Sensitizing Agents / pharmacokinetics
  • Radiation-Sensitizing Agents / therapeutic use*
  • Xenograft Model Antitumor Assays


  • Organic Chemicals
  • Poly(ADP-ribose) Polymerase Inhibitors
  • Radiation-Sensitizing Agents
  • GPI 15427