Radiosensitisation by pharmacological ascorbate in glioblastoma multiforme cells, human glial cells, and HUVECs depends on their antioxidant and DNA repair capabilities and is not cancer specific

Free Radic Biol Med. 2014 Sep:74:200-9. doi: 10.1016/j.freeradbiomed.2014.06.022. Epub 2014 Jun 30.


We previously showed that 5 mM ascorbate radiosensitized early passage radioresistant glioblastoma multiforme (GBM) cells derived from one patient tumor. Here we investigate the sensitivity of a panel of cell lines to 5 mM ascorbate and 6 Gy ionizing radiation, made up of three primary human GBM cells, three GBM cell lines, a human glial cell line, and primary human vascular endothelial cells. The response of different cells lines to ascorbate and/or radiation was determined by measuring viability, colony-forming ability, generation and repair of double-stranded DNA breaks (DSBs), cell cycle progression, antioxidant capacity and generation of reactive oxygen species. Individually, radiation and ascorbate both decreased viability and clonogenicity by inducing DNA damage, but had differential effects on cell cycle progression. Radiation led to G2/M arrest in most cells whereas ascorbate caused accumulation in S phase, which was moderately associated with poor DSB repair. While high dose ascorbate radiosensitized all cell lines in clonogenic assays, the sensitivity to radiation, high dose ascorbate, and combined treatment varied between cell lines. Normal glial cells were similar to GBM cells with respect to free radical scavenging potential and effect of treatment on DNA damage and repair, viability, and clonogenicity. Both GBM cells and normal cells coped equally poorly with oxidative stress caused by radiation and/or high dose ascorbate, dependent primarily on their antioxidant and DSB repair capacity.

Keywords: Antioxidant capacity; Cell cycle arrest; DNA repair; Glioblastoma multiforme; High dose ascorbate; Radiation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Ascorbic Acid / pharmacology*
  • Cell Line, Tumor
  • Cell Survival
  • Chemoradiotherapy / methods*
  • Colony-Forming Units Assay
  • DNA Repair / drug effects
  • DNA Repair / radiation effects
  • Endothelial Cells / drug effects
  • Endothelial Cells / physiology*
  • Endothelial Cells / radiation effects
  • G2 Phase Cell Cycle Checkpoints / drug effects
  • G2 Phase Cell Cycle Checkpoints / radiation effects
  • Glioblastoma / pathology
  • Glioblastoma / therapy*
  • Humans
  • Neuroglia / drug effects
  • Neuroglia / physiology*
  • Neuroglia / radiation effects
  • Oxidative Stress / drug effects
  • Oxidative Stress / radiation effects
  • Radiation, Ionizing
  • Radiation-Sensitizing Agents / pharmacology*
  • Reactive Oxygen Species / metabolism


  • Radiation-Sensitizing Agents
  • Reactive Oxygen Species
  • Ascorbic Acid