Sertindole, a potent antagonist at dopamine D₂ receptors, induces autophagy by increasing reactive oxygen species in SH-SY5Y neuroblastoma cells

Biol Pharm Bull. 2012;35(7):1069-75. doi: 10.1248/bpb.b12-00009.


Autophagy is associated with cell survival and cell death. Autophagy is implicated in the pathophysiology of various human diseases. In order to identify autophagy regulatory molecules, we screened a chemical drug library in SH-SY5Y cells and selected Sertindole as a potent autophagy inducer. Sertindole was developed as an antipsychotic drug for Schizophrenia. Sertindole treatment highly induced the formation of autophagosomes as well as LC3 conversion. Subsequently, Sertindole-induced autophagy was efficiently suppressed by down regulation of ATG5. Sertindole also increased reactive oxygen species (ROS) production, which contributes to autophagy-associated cell death in neuroblastoma cells. ROS scavengers such as N-acetylcysteine and Trolox suppressed not only ROS generation but also autophagy activation by Sertindole. These results suggest Sertindole induces autophagy and autophagy-associated cell death by ROS production in neuroblastoma cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcysteine / pharmacology
  • Antioxidants / pharmacology
  • Antipsychotic Agents / pharmacology*
  • Autophagy / drug effects*
  • Autophagy / physiology
  • Cell Line, Tumor
  • Chromans / pharmacology
  • Dopamine D2 Receptor Antagonists
  • Humans
  • Imidazoles / pharmacology*
  • Indoles / pharmacology*
  • Neuroblastoma
  • Reactive Oxygen Species / metabolism*
  • Receptors, Dopamine D2 / physiology


  • Antioxidants
  • Antipsychotic Agents
  • Chromans
  • Dopamine D2 Receptor Antagonists
  • Imidazoles
  • Indoles
  • Reactive Oxygen Species
  • Receptors, Dopamine D2
  • sertindole
  • 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid
  • Acetylcysteine