title: Selegiline reduces cisplatin-induced neuronal death in neuroblastoma cells.
abstract: Long-term administration of the monoamine oxidase (MAO)-B inhibitor selegiline may reduce neuronal death based on preclinical findings and reduce progression of chronic neurodegeneration due to outcomes of long-term clinical trials in patients with Parkinson's disease. Additional modes of action of this compound are immune system modulating and neurotrophic properties. We investigated the impact of simultaneous selegiline and cisplatin administration on the degree of cisplatin-induced cell death in SH-SY 5Y human neuroblastoma cells. We found a significantly reduced cell death rate after 50 and 74 hours after 2 hours lasting cisplatin exposure of SH-SY 5Y cells with additional selegiline treatment in comparison with cultures without selegiline. No previous incubation of cell cultures with selegiline was necessary to achieve this neuroprotective effect. We suggest that the neuroprotective effect of selegiline is predominantly associated with neurotrophic actions but not MAO-B inhibition, because SH-SY 5Y human neuroblastoma cells only contain MAO-A. Clinically, our findings support an early start of long-term treatment with selegiline in view of the various neurotoxin hypotheses and mechanisms of neuronal death in chronic neurodegenerative disorders.
authors.affiliation: Department of Neurology, St Josef Hospital, University of Bochum, Gudrunstr. 56, 44791 Bochum, Germany. thomas.mueller@ruhr-uni-bochum.de
authors.forename: Thomas
authors.initials: T
authors.lastname: Müller
authors.forename: Horst
authors.initials: H
authors.lastname: Przuntek
authors.forename: Meike
authors.initials: M
authors.lastname: Rieks
authors.forename: Anita
authors.initials: A
authors.lastname: Mackowiak
mesh_terms: D000970:Antineoplastic Agents / Q000037:antagonists & inhibitors / Q000633:toxicity; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000037:antagonists & inhibitors / Q000633:toxicity; D004347:Drug Interactions; D006801:Humans; D008995:Monoamine Oxidase / Q000187:drug effects* / Q000378:metabolism; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D009410:Nerve Degeneration / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D009447:Neuroblastoma; D019636:Neurodegenerative Diseases / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D012642:Selegiline / Q000494:pharmacology* / Q000627:therapeutic use; D013997:Time Factors
chemical_list: D000970:Antineoplastic Agents; D008996:Monoamine Oxidase Inhibitors; D018696:Neuroprotective Agents; D012642:Selegiline; D008995:Monoamine Oxidase; D002945:Cisplatin