Effect of lycopene and β-carotene on peroxynitrite-mediated cellular modifications

Abstract

Peroxynitrite formed by the reaction of superoxide and nitric oxide is a highly reactive species with a role in various pathological processes such as cancer, chronic inflammation, and cardiovascular and neurological diseases. In the present study, the effect of the carotenoids, lycopene and β-carotene, on peroxynitrite-mediated modifications in plasmid DNA as well as cellular DNA and proteins were investigated. In pUC18 plasmid DNA, these carotenoids strongly inhibited DNA strand breaks caused by peroxynitrite generated from 3-morpholinosydnonimine (SIN-1). SIN-1 was also used to determine effects on DNA damage and protein tyrosine nitration in Chinese hamster lung fibroblasts. SIN-1 dose-dependently increased nitration of proteins in cells above basal levels as determined by western blotting. This nitration was inhibited in the presence of the uric acid as well as lycopene. Physiological concentrations (0.31-10 μM) of lycopene and β-carotene also had protective effects on DNA damage, as measured by the comet assay. Lycopene significantly reduced DNA damage particularly, in the median range of concentrations (2.5 μM).The protective effects of lycopene and β-carotene could be due to their scavenging of reactive oxygen (ROS) and/or nitrogen species (RNS) as they reduce the amount of intracellular ROS/RNS produced following treatment with SIN-1 by as much as 47.5 and 42.4 %, respectively. The results obtained in this study suggest that carotenoids may alleviate some of the deleterious effects of peroxynitrite and possibly other reactive nitrogen species as well in vivo.

Multitargeted therapy of cancer by lycopene

“…Liu et al [26] investigated the subcellular localization of lycopene in prostate cancer cells treated with lycopene in cell culture, and determined that 81% was localized to the nucleus (55% in the nuclear membrane and 26% in the nuclear matrix). Localization of lycopene in the nucleus is consistent with the DNA protective effects exhibited by lycopene in several studies [23][24][25].…”

“…In cell culture, lycopene at 0.31 to 10 µM was shown to inhibit nitration of proteins and DNA strand breakage caused by peroxynitrite treatment of Chinese hamster lung fibroblasts [23]. Oxidative DNA damage caused by the redox-cycling of catechol-estrogens in plasmid DNA and Chinese hamster lung fibroblasts was also reduced by lycopene at 0.25 to 10 µM [24].…”

Lycopene protects the structure of the small intestine against gamma‐radiation‐induced oxidative stress

“…Lycopene -a carotenoid highly present in tomatoes and tomato products -was shown to scavenge ROS and reactive nitrogen species (RNS) (Muzandu et al, 2006) and to exhibit high singlet oxygen quenching ability . In this context, Rencuzogullari and Erdogan (2007) found that oral administration of lycopene reduces lipid peroxidation in cadmium-treated rats.…”

Protective Effect of Lycopene on Oxidative Stress and Cognitive Decline in Rotenone Induced Model of Parkinson’s Disease

“…It has been shown to quench peroxyl (LOO Á ) and superoxide radicals with high efficiency [18]. Lycopene and beta-carotene have been shown to scavenge Reactive oxygen species (ROS) and/or Reactive nitrogen species (RNS) and reduce the amount of intracellular ROS/RNS produced following treatment with 3-morpholinosydnonimine by as much as 47.5 and 42.4%, respectively [19]. In addition, lycopene has been observed to detoxify other reactive oxygen species such as OH -, O 2 -, peroxynitrite with high efficiency [20], which are produced in significant amounts in brain.…”