A radiosensitizing effect of artesunate in glioblastoma cells is associated with a diminished expression of the inhibitor of apoptosis protein survivin

Radiother Oncol. 2012 Jun;103(3):394-401. doi: 10.1016/j.radonc.2012.03.018. Epub 2012 May 3.


Background and purpose: Novel strategies to overcome an irradiation resistant phenotype may help to increase therapeutic efficacy in glioblastoma multiforme. The present study aimed to elucidate radiation sensitizing properties of artesunate, a semi synthetic derivate of artemisinin and to assess factors involved in this effect.

Materials and methods: LN229 and U87MG cells were treated with various concentrations of artesunate and radiation response was determined by a colony forming assay. Cell numbers, apoptosis induction, cell cycle distribution, and DNA repair following combined modality treatment were monitored by MTT-, caspase 3/7 assay, cytofluorometry, and γ-H2AX foci formation. Expression of survivin, survivin-GFP fusion protein, XIAP, cellular (c)IAP1 and cIAP2 was monitored by Western immunoblotting.

Results: Treatment of glioma cells with artesunate and irradiation resulted in an increased apoptotic fraction, pronounced G2/M arrest and increased DNA damage as demonstrated by an elevated amount of γ-H2AX foci/nucleus. Incubation with artesunate lowers survivin expression in a time and dose-dependent manner, whereas expression of XIAP, cIAP1 and cIAP2 was not affected. In clonogenic assays, treatment with artesunate revealed a significantly reduced surviving fraction, whereas stable over expression of a survivin-GFP protein reversed artesunate-mediated radiosensitization.

Conclusion: Artesunate selectively down regulates survivin that contributes to a radio-sensitization of glioma cells by an increased induction of apoptosis, cell cycle arrest, and a hampered DNA damage response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects
  • Artemisinins / pharmacology*
  • Artesunate
  • Brain Neoplasms / genetics
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / radiotherapy*
  • Cell Cycle / radiation effects
  • Cell Line, Tumor
  • Cell Survival / radiation effects
  • DNA Repair / drug effects
  • Dose-Response Relationship, Drug
  • Down-Regulation
  • Glioblastoma / genetics
  • Glioblastoma / metabolism
  • Glioblastoma / radiotherapy*
  • Humans
  • Inhibitor of Apoptosis Proteins / metabolism*
  • Neoplasm Proteins / metabolism
  • Radiation-Sensitizing Agents / pharmacology*
  • Survivin


  • Artemisinins
  • BIRC5 protein, human
  • Inhibitor of Apoptosis Proteins
  • Neoplasm Proteins
  • Radiation-Sensitizing Agents
  • Survivin
  • Artesunate