A chemical screen for medulloblastoma identifies quercetin as a putative radiosensitizer

Tonny Lagerweij, Lotte Hiddingh, Dennis Biesmans, Matheus H.W. Crommentuijn, Jacqueline Cloos, Xiao Nan Li, Mari Kogiso, Bakhos A. Tannous, W. Peter Vandertop, David P. Noske, Gertjan J.L. Kaspers, Tom Würdinger, Esther Hulleman*

*Corresponding author for this work

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

Treatment of medulloblastoma in children fails in approximately 30% of patients, and is often accompanied by severe late sequelae. Therefore, more effective drugs are needed that spare normal tissue and diminish long-term side effects. Since radiotherapy plays a pivotal role in the treatment of medulloblastoma, we set out to identify novel drugs that could potentiate the effect of ionizing radiation. Thereto, a small molecule library, consisting of 960 chemical compounds, was screened for its ability to sensitize towards irradiation. This small molecule screen identified the flavonoid quercetin as a novel radiosensitizer for the medulloblastoma cell lines DAOY, D283-med, and, to a lesser extent, D458-med at low micromolar concentrations and irradiation doses used in fractionated radiation schemes. Quercetin did not affect the proliferation of neural precursor cells or normal human fibroblasts. Importantly, in vivo experiments confirmed the radiosensitizing properties of quercetin. Administration of this flavonoid at the time of irradiation significantly prolonged survival in orthotopically xenografted mice. Together, these findings indicate that quercetin is a potent radiosensitizer for medulloblastoma cells that may be a promising lead for the treatment of medulloblastoma in patients.

Original languageEnglish (US)
Pages (from-to)35776-35788
Number of pages13
JournalOncotarget
Volume7
Issue number24
DOIs
StatePublished - 2016

Keywords

  • Medulloblastoma
  • Quercetin
  • Radiosensitizer
  • Screen
  • Small molecule

ASJC Scopus subject areas

  • Oncology

Fingerprint Dive into the research topics of 'A chemical screen for medulloblastoma identifies quercetin as a putative radiosensitizer'. Together they form a unique fingerprint.

  • Cite this

    Lagerweij, T., Hiddingh, L., Biesmans, D., Crommentuijn, M. H. W., Cloos, J., Li, X. N., Kogiso, M., Tannous, B. A., Vandertop, W. P., Noske, D. P., Kaspers, G. J. L., Würdinger, T., & Hulleman, E. (2016). A chemical screen for medulloblastoma identifies quercetin as a putative radiosensitizer. Oncotarget, 7(24), 35776-35788. https://doi.org/10.18632/oncotarget.7980