Lycopene attenuates alcoholic apoptosis in HepG2 cells expressing CYP2E1.
To test the hypothesis that ethanol-induced hepatic apoptosis is secondary to the oxidative stress generated by cytochrome P4502E1 (CYP2E1), we assessed the effects of the carotenoid lycopene, a potent antioxidant extracted from tomatoes, on oxidative stress and apoptosis in HepG2 cells overexpressing CYP2E1 (2E1 cells). These were exposed for 5 days to 100mM ethanol and 10 microM lycopene or an equal volume of placebo (vehicle). Ethanol significantly increased apoptosis measured by flow cytometry and by TUNEL assay. This was accompanied by an ethanol-induced oxidative stress: hydrogen peroxide production was significantly increased and mitochondrial GSH was strikingly decreased. Both were restored by lycopene, with a significant decrease in apoptosis. The placebo had no protective effect. In conclusion, Lycopene opposes the ethanol-induced oxidative stress and apoptosis in 2E1 cells. The parallelism between these effects suggests a causal link. Furthermore, these beneficial effects and the innocuity of lycopene now justify an in vivo trial.
Xu
Youqing
Y
Section of Liver Disease & Nutrition, Alcohol Research and Treatment Center, Veterans Affairs Medical Center & Mt Sinai School of Medicine, 130 West Kingsbridge Road, Bronx, NY, USA.
Leo
Maria A
MA
Lieber
Charles S
CS
D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002338:Carotenoids / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics / Q000378:metabolism*; D000431:Ethanol / Q000037:antagonists & inhibitors*; D015870:Gene Expression; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D000077276:Lycopene; D008928:Mitochondria / Q000378:metabolism; D018384:Oxidative Stress; D014161:Transduction, Genetic; D014407:Tumor Cells, Cultured
D000975:Antioxidants; D002338:Carotenoids; D000431:Ethanol; D006861:Hydrogen Peroxide; D019392:Cytochrome P-450 CYP2E1; D005978:Glutathione; D000077276:Lycopene