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.
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.
Authors: M Venere; P Hamerlik; Q Wu; R D Rasmussen; L A Song; A Vasanji; N Tenley; W A Flavahan; A B Hjelmeland; J Bartek; J N Rich Journal: Cell Death Differ Date: 2013-10-11 Impact factor: 15.828
Authors: Rob Noorlag; Pauline M W van Kempen; Cathy B Moelans; Rick de Jong; Laura E R Blok; Ronald Koole; Wilko Grolman; Paul J van Diest; Robert J J van Es; Stefan M Willems Journal: Epigenetics Date: 2014-07-08 Impact factor: 4.528
Authors: Li Wang; Kathy A Mason; K Kian Ang; Thomas Buchholz; David Valdecanas; Anjili Mathur; Carolyn Buser-Doepner; Carlo Toniatti; Luka Milas Journal: Invest New Drugs Date: 2011-11-30 Impact factor: 3.850
Authors: M Damek-Poprawa; A Volgina; J Korostoff; T P Sollecito; M S Brose; B W O'Malley; S O Akintoye; J M DiRienzo Journal: J Dent Res Date: 2011-01-10 Impact factor: 6.116