Radiosensitization of human lung cancer cells by the novel purine-scaffold Hsp90 inhibitor, PU-H71

Int J Mol Med. 2014 Mar;33(3):559-64. doi: 10.3892/ijmm.2013.1594. Epub 2013 Dec 19.


The molecular chaperone heat shock protein 90 (Hsp90) is involved in the maturation and stabilization of a wide range of oncogenic client proteins for oncogenesis and malignant cell proliferation, which renders this protein a promising target in the development of cancer therapeutics. PU-H71 is a purine-scaffold Hsp90 inhibitor with less toxicity in normal cells than in cancer cells. In this study, we examined the in vitro radiosensitizing activity and molecular mechanisms of action of PU-H71 in human lung cancer cell lines. PU-H71 enhanced the sensitivity of the SQ-5 and A549 cancer cells to radiation. When the cancer cells were pre-treated with PU-H71, the repair of DNA double-strand breaks (DSBs) was markedly inhibited after irradiation compared with the cells that were not pre-treated with PU-H71, as evaluated by counting the foci of phosphorylated histone H2AX (γ-H2AX). We further demonstrated that post-irradiation, PU-H71 inhibited Rad51 foci formation, a critical protein for the homologous recombination pathway of DNA DSB repair. These data indicate that targeting Hsp90 with PU-H71 may be novel therapeutic strategy for radioresistant carcinomas.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Benzodioxoles / administration & dosage*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Proliferation / radiation effects
  • DNA Repair / drug effects
  • DNA Repair / radiation effects
  • HSP90 Heat-Shock Proteins / antagonists & inhibitors
  • HSP90 Heat-Shock Proteins / biosynthesis
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / pathology
  • Lung Neoplasms / radiotherapy
  • Purines / administration & dosage*
  • Purines / metabolism
  • Radiation Tolerance / drug effects*


  • Benzodioxoles
  • HSP90 Heat-Shock Proteins
  • Purines
  • 9H-purine-9-propanamine, 6-amino-8-((6-iodo-1,3-benzodioxol-5-yl)thio)-N-(1-methylethyl)-
  • purine