Role of undecan-2-one on ethanol-induced apoptosis in HepG2 cells.
Based on the reduced expression of ethanol-oxidizing enzymes in human hepatocellular carcinoma (HepG2) cells, we analyzed the role of nonoxidative metabolites in ethanol-induced apoptosis in HepG2 cells. For this purpose, an analysis of volatile metabolites of ethanol using ion-mobility spectrometry and gas chromatography-mass spectrometry was performed. HepG2 cells exposed to 1 mmol/L ethanol exhibited significant synthesis of undecan-2-one compared to untreated cells. Undecan-2-one is a fatty acid ethyl ester metabolite synthesized through a nonoxidative pathway. Undecan-2-one had a dose-dependent cytotoxic effect on HepG2 cells as shown by release of lactate dehydrogenase (LDH). The most notable finding of this study was the potentiation of ethanol-induced apoptosis demonstrated by an increased apoptotic rate induced by undecan-2-one in ethanol-treated HepG2 cells. The data presented in this study contribute to the better understanding of the molecular mechanisms of ethanol exposure at low concentration in HepG2 cells, a human hepatocellular carcinoma-derived cell line.
Castaneda
F
F
Laboratory for Molecular Pathobiochemistry and Clinical Research, Max Planck Institute for Molecular Physiology, Dortmund, Germany. francisco.castaneda@mpi-dortmund.mpg.de
Zimmermann
D
D
Nolte
J
J
Baumbach
J I
JI
D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D000431:Ethanol / Q000494:pharmacology*; D006801:Humans; D007659:Ketones / Q000378:metabolism* / Q000494:pharmacology; D013058:Mass Spectrometry; D013997:Time Factors
D007659:Ketones; D000431:Ethanol; C526928:undecan-2-one