Anandamide induces apoptosis of PC-12 cells: involvement of superoxide and caspase-3

FEBS Lett. 2000 Apr 21;472(1):39-44. doi: 10.1016/s0014-5793(00)01425-3.


Anandamide (arachidonoylethanolamide), an endogenous cannabinoid receptor ligand has been suggested to have physiological role in mammalian nervous system. However, little is known about the role of anandamide on neuronal cells. Here, we demonstrate that anandamide causes death of PC-12 cells, showing marked DNA condensation and fragmentation, appearance of cells at sub-G(0)/G(1) and redistribution of phosphatidyl serine, the hallmark features of apoptosis. Anandamide raised intracellular superoxide level and CPP32-like protease activity in PC-12 cells markedly. Furthermore, antioxidant N-acetyl cysteine prevented anandamide-induced superoxide anion formation and cell death, implying that intracellular superoxide is a novel mediator of anandamide-induced apoptosis of PC-12 cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcysteine / pharmacology
  • Animals
  • Apoptosis / physiology*
  • Arachidonic Acids / antagonists & inhibitors
  • Arachidonic Acids / pharmacology
  • Arachidonic Acids / physiology*
  • Caspase 3
  • Caspases / metabolism*
  • Cell Survival
  • Endocannabinoids
  • PC12 Cells
  • Polyunsaturated Alkamides
  • Rats
  • Superoxides / metabolism*


  • Arachidonic Acids
  • Endocannabinoids
  • Polyunsaturated Alkamides
  • Superoxides
  • Casp3 protein, rat
  • Caspase 3
  • Caspases
  • anandamide
  • Acetylcysteine