Selegiline reduces cisplatin-induced neuronal death in neuroblastoma cells

Neurol Res. 2008 May;30(4):417-9. doi: 10.1179/016164107X251619. Epub 2008 Jan 30.

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.

MeSH terms

  • Antineoplastic Agents / antagonists & inhibitors
  • Antineoplastic Agents / toxicity
  • Cell Death / drug effects
  • Cell Death / physiology
  • Cell Line, Tumor
  • Cisplatin / antagonists & inhibitors
  • Cisplatin / toxicity
  • Drug Interactions
  • Humans
  • Monoamine Oxidase / drug effects*
  • Monoamine Oxidase / metabolism
  • Monoamine Oxidase Inhibitors / pharmacology
  • Monoamine Oxidase Inhibitors / therapeutic use
  • Nerve Degeneration / chemically induced
  • Nerve Degeneration / drug therapy*
  • Nerve Degeneration / physiopathology
  • Neuroblastoma
  • Neurodegenerative Diseases / drug therapy
  • Neurodegenerative Diseases / metabolism
  • Neurodegenerative Diseases / physiopathology
  • Neurons / drug effects*
  • Neurons / metabolism
  • Neuroprotective Agents / pharmacology*
  • Neuroprotective Agents / therapeutic use
  • Selegiline / pharmacology*
  • Selegiline / therapeutic use
  • Time Factors

Substances

  • Antineoplastic Agents
  • Monoamine Oxidase Inhibitors
  • Neuroprotective Agents
  • Selegiline
  • Monoamine Oxidase
  • Cisplatin