Repurposing of Idebenone as a potential anticancer agent

Elisabetta Damiani, Raif Yuecel, Heather M. Wallace* (Corresponding Author)

*Corresponding author for this work

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Glioblastoma (GB) represents the most common and aggressive form of malignant primary brain tumour associated with high rates of morbidity and mortality. In the present study, we considered the potential use of idebenone (IDE), a Coenzyme Q10 analogue, as a novel chemotherapeutic agent for GB. On two GB cell lines, U373MG and U87MG, IDE decreased the viable cell number and enhanced the cytotoxic effects of two known anti-proliferative agents: temozolomide and oxaliplatin. IDE also affected the clonogenic and migratory capacity of both GB cell lines, at 25 and 50 µM, a concentration equivalent to that transiently reached in plasma after oral intake that is deemed safe for humans. p21 protein expression was decreased in both cell lines, indicating that IDE likely exerts its effects through cell cycle dysregulation, and this was confirmed in U373MG cells only by flow cytometric cell cycle analysis which showed S-phase arrest. Caspase-3 protein expression was also significantly decreased in U373MG cells indicating IDE-induced apoptosis that was confirmed by flow cytometric Annexin V/propidium iodide staining. No major decrease in caspase-3 expression was observed in U87MG cells nor apoptosis as observed by flow cytometry analysis. Overall, the present study demonstrates that IDE has potential as an anti-proliferative agent for GB by interfering with several features of glioma pathogenesis such as proliferation and migration, and hence might be a drug that could be repurposed for aiding cancer treatments. Furthermore, the synergistic combinations of IDE with other agents aimed at different pathways involved in this type of cancer are promising.

Original languageEnglish
Pages (from-to)245-259
Number of pages15
JournalBiochemical Journal
Issue number2
Early online date25 Jan 2019
Publication statusPublished - Jan 2019

Bibliographical note

Funding. E.D. was funded by an internal research grant from the Polytechnic University of the Marche provided by MIUR (Italian Ministry of University and Research). Funding for FACS experiments was provided by grant code no. RO10014-13 from the Cell, Developmental and Cancer Biology Research Programme, University of Aberdeen.


  • Idebenone
  • glioblastoma cells
  • anti-proliferation
  • anti-migration
  • P21(WAF1)


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