Hedgehog signaling sensitizes glioma stem cells to endogenous nano-irradiation

Agnieszka Morgenroth*, Andreas T J Vogg, Katja Ermert, Boris Zlatopolskiy, Felix M Mottaghy

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


The existence of therapy resistant glioma stem cells is responsible for the high recurrence rate and incurability of glioblastomas. The Hedgehog pathway activity plays an essential role for self-renewal capacity and survival of glioma stem cells. We examined the potential of the Sonic hedgehog ligand for sensitizing of glioma stem cells to endogenous nano-irradiation. We demonstrate that the Sonic hedgehog ligand preferentially and efficiently activated glioma stem cells to enter the radiation sensitive G2/M phase. Concomitant inhibition of de novo thymidine synthesis with fluorodeoxyuridine and treatment with the Auger electron emitting thymidine analogue 5-[I-125]-Iodo-4'-thio-2'-deoxyuridine ([I-125]ITdU) leads to a fatal nano-irradiation in sensitized glioma stem cells. Targeting of proliferating glioma stem cells with DNA-incorporated [I-125]ITdU efficiently invokes the intrinsic apoptotic pathway despite active DNA repair mechanisms. Further, [I-125]ITdU completely inhibits survival of glioma stem cells in vitro. Analysis of non-stem glioblastoma cells and normal human astrocytes reveals that glioma stem cells differentially respond to Sonic hedgehog ligand. These data demonstrate a highly efficient and controllable single-cell kill therapeutic model for targeting glioma stem cells.

Original languageEnglish
Pages (from-to)5483-5493
Number of pages11
Issue number14
Publication statusPublished - 30 Jul 2014


  • Apoptosis
  • Brain Neoplasms
  • Cell Line, Tumor
  • Cell Proliferation
  • Deoxyuridine
  • Glioblastoma
  • Hedgehog Proteins
  • Humans
  • Iodine Radioisotopes
  • Neoplastic Stem Cells
  • Radiation Tolerance
  • Radiopharmaceuticals
  • Signal Transduction

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