title: Idebenone induces apoptotic cell death in the human dopaminergic neuroblastoma SHSY-5Y cells.
abstract: Idebenone is a coenzyme Q10 analog and an antioxidant that has been used clinically to treat Friedreich Ataxia. Being an antioxidant, idebenone could have potential therapeutic potential to treat other neurodegenerative diseases such as Parkinson's disease in which oxidative stress plays a role in their pathogenesis. But whether idebenone can be used to treat Parkinson's disease has not been evaluated. In this study, we found that exposure of the dopaminergic neuroblastoma SHSY-5Y cells to 1-10 μM idebenone for 72 h had no effect on the cell viability revealed by trypan blue exclusion assay and MTT assay. However, cells exposed to 25 μM or higher concentrations of idebenone showed extensive trypan blue-positive staining and significant reduction in cell viability revealed by MTT assay indicating that most of the cells were no longer viable. Idebenone-induced cell death was characterized by genomic DNA fragmentation and accumulation of cytochrome c in the cytosol indicating that the death was apoptotic in nature. In addition, idebenone induced an increase in the total RNA of the pro-apoptosis protein BAX, it also increased the caspase-3 activity in the cell lysates when compared with the untreated control cells or cells exposed to 10 μM or lower concentrations of idebenone. The detrimental effect of idebenone was attenuated by glutathione, an antioxidant, suggesting that oxidative stress contributed to the idebenone-induced cell death. In conclusion, our results suggest that antioxidant idebenone induced apoptosis when used in high concentrations.
authors.affiliation: The Parkinson's and Movement Disorder Research Laboratory, Long Beach Memorial Medical Center, 2801 Atlantic Ave., Long Beach, CA, USA. kktai@yahoo.com
authors.forename: Kwok-Keung
authors.initials: KK
authors.lastname: Tai
authors.forename: L
authors.initials: L
authors.lastname: Pham
authors.forename: D D
authors.initials: DD
authors.lastname: Truong
mesh_terms: D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism; D053938:DNA Fragmentation / Q000187:drug effects; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D009447:Neuroblastoma / Q000473:pathology; D013778:Tetrazolium Salts; D013844:Thiazoles; D013997:Time Factors; D014343:Trypan Blue; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D013778:Tetrazolium Salts; D013844:Thiazoles; D014451:Ubiquinone; D045304:Cytochromes c; D053148:Caspase 3; C022616:thiazolyl blue; D005978:Glutathione; C036619:idebenone; D014343:Trypan Blue; D004298:Dopamine