Effects of apigenin, lycopene and astaxanthin on 7 beta-hydroxycholesterol-induced apoptosis and Akt phosphorylation in U937 cells.
Oxysterols arise from the enzymic or non-enzymic oxidation of cholesterol and have been shown to be cytotoxic to certain cell lines. In particular, apoptosis induced by the oxysterol 7 beta-hydroxycholesterol (7 beta-OH) has been associated with the generation of oxidative stress, cytochrome c release and caspase activation. Due to the fundamental importance of apoptosis in pathological processes, the identification of substances capable of modulating this form of cell death is now actively researched. The objective of the present study was to investigate if apigenin, lycopene and astaxanthin could inhibit 7 beta-OH-induced apoptosis in U937 cells. Pretreatment with 0.1 mum-astaxanthin protected against apoptosis, while lycopene did not oppose the adverse effects of 7 beta-OH. At low concentrations, apigenin did not protect against oxysterol-induced apoptosis; however, at higher concentrations it intensified cell death. Additionally, we investigated the effect of 7 beta-OH, apigenin and astaxanthin on the activation of the serine threonine kinase Akt (phosphorylated Akt:Akt ratio) to determine whether the effect on cell viability and growth was linked to the Akt signalling pathway. Akt activation was decreased in the oxysterol-treated cells compared with control cells; however, this did not attain significance. Interestingly, activation of Akt was significantly reduced compared with control cells following incubation with apigenin and astaxanthin both in the absence and in the presence of 7 beta-OH. Our data suggest that apigenin, lycopene and astaxanthin failed to protect against 7 beta-OH-induced apoptosis, and the decrease in cell viability and the increase in apoptotic nuclei induced by the antioxidants appear to be associated with down regulation of Akt activity.
Lordan
Sinéad
S
Department of Food and Nutritional Sciences, University College, Cork, Republic of Ireland.
O'Neill
Cora
C
O'Brien
Nora M
NM
D000975:Antioxidants / Q000494:pharmacology*; D047310:Apigenin / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D002338:Carotenoids / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D053938:DNA Fragmentation; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006888:Hydroxycholesterols / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D000077276:Lycopene; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D020298:U937 Cells; D024341:Xanthophylls / Q000494:pharmacology
D000975:Antioxidants; D006888:Hydroxycholesterols; D024341:Xanthophylls; D002338:Carotenoids; C011724:cholest-5-en-3 beta,7 alpha-diol; D047310:Apigenin; C005948:astaxanthine; D051057:Proto-Oncogene Proteins c-akt; D000077276:Lycopene