Arachidonic acid-induced apoptosis in rat hepatoma AS-30D cells is mediated by reactive oxygen species.
Arachidonic acid at micromolar concentrations produced a drastic increase of the generation of reactive oxygen species (ROS) in rat hepatoma AS-30D cells cultivated in vitro along with an increase in the incidence of apoptotic cell death. Both processes were prevented by trolox, a water-soluble tocopherol derivative, and tempol, a known antioxidative agent. A synthetic hybrid of lipoic acid and trolox or preincubation with N-acetylcysteine were less effective. Preincubation of the cells with etomoxir, a known highly specific irreversible inhibitor of carnitine-palmitoyltransferase I, partly decreased the ROS formation induced by arachidonic acid but it did not affect the increase in apoptosis. Cumulatively, these results indicate that apoptosis induced in hepatoma cells by arachidonic acid is mediated by ROS. They also suggest that this effect is due to arachidonic acid as such and not to its mitochondrial oxidative metabolites.
Dymkowska
Dorota
D
Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warszawa, Poland.
Wojtczak
Lech
L
D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D016718:Arachidonic Acid / Q000494:pharmacology* / Q000627:therapeutic use; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy*; D045744:Cell Line, Tumor; D002839:Chromans / Q000494:pharmacology; D003497:Cyclic N-Oxides / Q000494:pharmacology; D004852:Epoxy Compounds / Q000494:pharmacology; D008113:Liver Neoplasms / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013113:Spin Labels
D000975:Antioxidants; D002839:Chromans; D003497:Cyclic N-Oxides; D004852:Epoxy Compounds; D017382:Reactive Oxygen Species; D013113:Spin Labels; D016718:Arachidonic Acid; C054207:etomoxir; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid; C001803:tempol; D000111:Acetylcysteine