Repurposing of Idebenone as a potential anticancer agent

Glioblastoma (GB) represents the most common and aggressive form of malignant primary brain tumour associated with high rates of morbidity and mortality. In this study we considered the potential use of idebenone, a Coenzyme Q10 analogue, as a novel chemotherapeutic agent for GB. On two GB cell lines, U373MG and U87MG, idebenone decreased the viable cell number and enhanced the cytotoxic effects of two known anti-proliferative agents: temozolomide and oxaliplatin. Idebenone also affected the clonogenic and migratory capacity of both GB cell lines, at 25 uM and 50 uM, 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 idebenone 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 idebenone-induced apoptosis that was confirmed by flow cytometric Annexin V/PI 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 idebenone 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 idebenone with other agents aimed at different pathways involved in this type of cancer is promising.