Lycopene prevents 7-ketocholesterol-induced oxidative stress, cell cycle arrest and apoptosis in human macrophages.
The present study was undertaken to examine whether lycopene is able to counteract 7-ketocholesterol (7-KC)-induced oxidative stress and apoptosis in human macrophages. Human THP-1 macrophages were exposed to 7-KC (10-25 microM) alone and in combination with lycopene (0.5-2 microM), and we monitored changes in cell oxidative status [reactive oxygen species (ROS) production, NOX-4, hsp70 and hsp90 expressions, 8-OHdG formation] and in cell proliferation and apoptosis. After 24 h of treatment, lycopene significantly reduced the increase in ROS production and in 8-OHdG formation induced by the oxysterol in a dose-dependent manner. Moreover, the carotenoid strongly prevented the increase of NOX-4, hsp70 and hsp90 expressions as well as the phosphorylation of the redox-sensitive p38, JNK and ERK1/2 induced by the oxysterol. The attenuation of 7-KC-induced oxidative stress by lycopene coincided with a normalization of cell growth in human macrophages. Lycopene prevented the arrest in G0/G1 phase of cell cycle induced by the oxysterol and counteracted the increased expression of p53 and p21. Concomitantly, it inhibited 7-KC-induced apoptosis, by limiting caspase-3 activation and the modulatory effects of 7-KC on AKT, Bcl-2, Bcl-xL and Bax. Comparing the effects of lycopene, beta-carotene and (5Z)-lycopene on ROS production, cell growth and apoptosis show that lycopene and its isomer were more effective than beta-carotene in counteracting the dangerous effects of 7-KC in human macrophages. Our study suggests that lycopene may act as a potential antiatherogenic agent by preventing 7-KC-induced oxidative stress and apoptosis in human macrophages.
Palozza
Paola
P
Institute of General Pathology, Catholic University School of Medicine, 1 00168 Rome, Italy. p.palozza@rm.unicatt.it
Simone
Rossella
R
Catalano
Assunta
A
Boninsegna
Alma
A
Böhm
Volker
V
Fröhlich
Kati
K
Mele
Maria Cristina
MC
Monego
Giovanni
G
Ranelletti
Franco O
FO
D000080242:8-Hydroxy-2'-Deoxyguanosine; D017209:Apoptosis / Q000187:drug effects*; D002338:Carotenoids / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D002478:Cells, Cultured; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000096:biosynthesis; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis; D018841:HSP90 Heat-Shock Proteins / Q000096:biosynthesis; D006801:Humans; D007653:Ketocholesterols / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000077276:Lycopene; D008264:Macrophages / Q000187:drug effects; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases / Q000096:biosynthesis; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism
D018840:HSP70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; D007653:Ketocholesterols; D017382:Reactive Oxygen Species; D002338:Carotenoids; D000080242:8-Hydroxy-2'-Deoxyguanosine; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases; C498910:NOX4 protein, human; D003849:Deoxyguanosine; C003001:7-ketocholesterol; D000077276:Lycopene