Antioxidant and pro-oxidant effects of lycopene in comparison with β-carotene on oxidant-induced damage in Hs68 cells

Lycopene has become a focal point in recent research following clinical trials that suggest that β-carotene may promote lung cancer in smokers. Because lycopene only differs from β-carotene in lacking the β-ionone structure, and β-carotene is known to have pro-oxidant activity in vitro, we sought to determine whether lycopene might also have pro-oxidant activity in vitro in comparison with β-carotene. Human foreskin fibroblasts (Hs68 cells) were first enriched with 10 and 20 μM lycopene or β-carotene for 1 hr followed by incubation with various oxidants. Lipid peroxidation was measured as thiobarbituric acid-reactive substances (TBARS) released into the medium and DNA damage was measured as formation of comet and 8-hydroxy-2′-deoxyguanosine. The results showed that lycopene at 20 μM significantly decreased levels of TBARS induced by ferric nitrilotriacetate (Fe/NTA) but enhanced levels of TBARS induced by a lipid-soluble radical generator (2,2′-azobis[2,4-dimethylvaleronitrile]; AMVN). Both the antioxidant and pro-oxidant effects of lycopene tended to be dose-dependent. β-Carotene at 20 μM did not significantly decrease TBARS induced by Fe/NTA but significantly increased TBARS induced by AMVN. Lipid peroxidation induced by a water-soluble radical generator 2,2’-azobis(2-amidinopropane)dihydrochloride was not significantly affected by either lycopene or β-carotene. Neither lycopene nor β-carotene affected DNA damage or changes in cell morphology induced by any of the three oxidants tested. The present study in Hs68 cells demonstrates that lycopene can be either an antioxidant or a pro-oxidant depending on the oxidants used, and that lycopene and β-carotene behave similarly under the in vitro oxidative conditions. Although it is unclear whether lycopene may have pro-oxidant activity in vivo, our results caution that it may be premature to undertake clinical trials with lycopene.