Journal of Neuro-Oncology

, Volume 105, Issue 3, pp 485–498

Ethynyldeoxyuridine (EdU) suppresses in vitro population expansion and in vivo tumor progression of human glioblastoma cells

  • Heather H. Ross
  • Maryam Rahman
  • Lindsay H. Levkoff
  • Sebastien Millette
  • Teresa Martin-Carreras
  • Erin M. Dunbar
  • Brent A. Reynolds
  • Eric D. Laywell
Laboratory Investigation - Human/Animal Tissue

DOI: 10.1007/s11060-011-0621-6

Cite this article as:
Ross, H.H., Rahman, M., Levkoff, L.H. et al. J Neurooncol (2011) 105: 485. doi:10.1007/s11060-011-0621-6

Abstract

Thymidine analogs (TAs) are synthetic nucleosides that incorporate into newly synthesized DNA. Halogenated pyrimidines (HPs), such as bromodeoxyuridine (BrdU), are a class of TAs that can be detected with antibodies and are commonly used for birthdating individual cells and for assessing the proliferative index of cell populations. It is well established that HPs can act as radiosensitizers when incorporated into DNA chains, but they are generally believed not to impair normal cell function in the absence of secondary stressors. However, we and others have shown that HP incorporation leads to a sustained suppression of cell cycle progression in mammalian cells, resulting in cellular senescence in somatic cells. In addition, we have shown that HP incorporation results in delayed tumor progression in a syngeneic rat model of glioma. Here we examine ethynyldeoxyuridine (EdU), a newly developed and alkylated TA, for its anti-cancer activity, both in vitro and in vivo. We show that EdU, like HPs, leads to a severe reduction in the proliferation rate of normal and transformed cells in vitro. Unlike HPs, however, EdU incorporation also causes DNA damage resulting in the death of a substantial subset of treated cells. When administered over an extended time as a monotherapy to mice bearing subcutaneous xenografts of human glioblastoma multiforme tumors, EdU significantly reduces tumor volume and increases survival without apparent significant toxicity. These results, combined with the fact that EdU readily crosses the blood–brain barrier, support the continued investigation of EdU as a potential therapy for malignant brain tumors.

Keywords

Glioblastoma multiforme (GBM)ProliferationEthynyldeoxyuridine (EdU)Thymidine analog

Supplementary material

11060_2011_621_MOESM1_ESM.doc (173 kb)
Supplementary material 1 (DOC 173 kb)

Copyright information

© Springer Science+Business Media, LLC. 2011

Authors and Affiliations

  • Heather H. Ross
    • 1
  • Maryam Rahman
    • 2
  • Lindsay H. Levkoff
    • 3
  • Sebastien Millette
    • 2
  • Teresa Martin-Carreras
    • 1
  • Erin M. Dunbar
    • 2
    • 4
    • 5
    • 6
  • Brent A. Reynolds
    • 2
    • 5
    • 6
  • Eric D. Laywell
    • 7
  1. 1.Department of Physical TherapyUniversity of FloridaGainesvilleUSA
  2. 2.Department of NeurosurgeryUniversity of FloridaGainesvilleUSA
  3. 3.Department of Anatomy and Cell Biology, College of MedicineUniversity of FloridaGainesvilleUSA
  4. 4.Preston A. Wells, Jr Center for Brain Tumor TherapyGainesvilleUSA
  5. 5.McKnight Brain InstituteUniversity of FloridaGainesvilleUSA
  6. 6.UF Shands Cancer CenterUniversity of FloridaGainesvilleUSA
  7. 7.Department of Biomedical SciencesFlorida State University College of MedicineTallahasseeUSA