Sertindole, a potent antagonist at dopamine D₂ receptors, induces autophagy by increasing reactive oxygen species in SH-SY5Y neuroblastoma cells.
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.
Graduate School of East-West Medical Science, Kyung Hee University, Gyeoggi-do 446-701, Korea.
Ji Hyun
JH
Shin
So Jung
SJ
Park
Eun Sung
ES
Kim
Yoon Kyung
YK
Jo
Jungwoo
J
Hong
Dong-Hyung
DH
Cho
D000111:Acetylcysteine / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001343:Autophagy / Q000187:drug effects* / Q000502:physiology; D045744:Cell Line, Tumor; D002839:Chromans / Q000494:pharmacology; D065127:Dopamine D2 Receptor Antagonists; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology*; D009447:Neuroblastoma; D017382:Reactive Oxygen Species / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000502:physiology
D000975:Antioxidants; D014150:Antipsychotic Agents; D002839:Chromans; D065127:Dopamine D2 Receptor Antagonists; D007093:Imidazoles; D007211:Indoles; D017382:Reactive Oxygen Species; D017448:Receptors, Dopamine D2; C066304:sertindole; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid; D000111:Acetylcysteine