In vitro: |
Clin Exp Pharmacol Physiol. 2015 Jun;42(6):632-9. | Lycopene inhibits cyclic strain-induced endothelin-1 expression through the suppression of reactive oxygen species generation and induction of heme oxygenase-1 in human umbilical vein endothelial cells.[Pubmed: 25932745] | Lycopene is the most potent active antioxidant among the major carotenoids, and its use has been associated with a reduced risk for cardiovascular disease (CVD). This study investigated the effects of Lycopene on cyclic strain-induced ET-1 gene expression in human umbilical vein endothelial cells (HUVECs) and identified the signal transduction pathways that are involved in this process. METHODS AND RESULTS: Cultured HUVECs were exposed to cyclic strain (20% in length, 1 Hz) in the presence or absence of Lycopene. Lycopene inhibited strain-induced ET-1 expression through the suppression of reactive oxygen species (ROS) generation through attenuation of p22(phox) mRNA expression and NAD(P)H oxidase activity. Furthermore, Lycopene inhibited strain-induced ET-1 secretion by reducing ROS-mediated extrace-llular signal-regulated kinase (ERK) phosphorylation. Conversely, Lycopene treatment enhanced heme oxygenase-1 (HO-1) gene expression through the activation of phosphoinositide 3-kinase (PI3K)/Akt pathway, followed by induction of the nuclear factor erythroid 2-related factor 2 (Nrf2) nuclear translocation; in addition, HO-1 silencing partially inhibited the repressive effects of Lycopene on strain-induced ET-1 expression. CONCLUSIONS: In summary, our study showed, for the first time, that Lycopene inhibits cyclic strain-induced ET-1 gene expression through the suppression of ROS generation and induction of HO-1 in HUVECs.Therefore, this study provides new valuable insight into the molecular pathways that may contribute to the proposed beneficial effects of Lycopene on the cardiovascular system. | Ultrason Sonochem. 2015 Nov;27:586-591. | Effect of high power low frequency ultrasound processing on the stability of lycopene.[Pubmed: 25921608] | The stability of Lycopene was evaluated after application of high power low frequency ultrasound. METHODS AND RESULTS: The study was carried out on a solution containing pure Lycopene to evaluate the direct effect of ultrasound on Lycopene and on tomato purée to evaluate the direct and indirect effects of ultrasound application within a food matrix. Power densities ranging from 55 to 5000 W/L and temperatures ranging from 23°C (ambient) to 60°C were evaluated. The experiments on pure Lycopene showed that the application of ultrasound did not have any direct effect over Lycopene. However, the retention of Lycopene in tomato puree has decreased indicating an indirect effect on Lycopene stability caused by high concentration of hydrogen peroxide and the activation of peroxidase enzymes leading to the reduction of ascorbic acid and its regenerative action towards Lycopene. | Curr Med Chem. 2011;18(8):1146-63. | Lycopene and cardiovascular diseases: an update.[Pubmed: 21291369] | Cardiovascular disease (CVD) is the leading cause of death in Western societies and accounts for up to a third of all deaths worldwide. In comparison to the Northern European or other Western countries, the Mediterranean area has lower rates of mortality from cardiovascular diseases and cancer, and this is attributed, at least in part, to the so-called Mediterranean diet, which is rich in plantderived bioactive phytochemicals. Identification of the active constituents of the Mediterranean diet is therefore crucial to the formulation of appropriate dietary guidelines. METHODS AND RESULTS: Lycopene is a natural carotenoid found in tomato, an essential component of the Mediterranean diet, which, although belonging to the carotenoid family, does not have pro-vitamin A activity but many other biochemical functions as an antioxidant scavenger, hypolipaemic agent, inhibitor of pro-inflammatory and pro-thrombotic factors, thus potentially of benefit in CVD. In particular, the review intends to conduct a systematic analysis of the literature (epidemiological studies and interventional trials) in order to critically evaluate the association between Lycopene (or tomato products) supplementation and cardiovascular diseases and/or cardiovascular disease risk factors progression, and to prepare provision of evidence-based guidelines for patients and clinicians. Several reports have appeared in support of the role of Lycopene in the prevention of CVD, mostly based on epidemiological studies showing a dose-response relationship between Lycopene and CVD. A less clear and more complex picture emerges from the interventional trials, where several works have reported conflicting results. CONCLUSIONS: Although many aspects of Lycopene in vivo metabolism, functions and clinical indications remain to be clarified, supplementation of low doses of Lycopene has been already suggested as a preventive measure for contrasting and ameliorating many aspects of CVD. | 2016 Jul;37(7):9375-85. | Lycopene acts through inhibition of IκB kinase to suppress NF-κB signaling in human prostate and breast cancer cells[Pubmed: 26779636] | We studied the effect of the potent dietary antioxidant Lycopene on multiple points along the nuclear factor kappa B (NF-κB) signaling pathway in prostate and breast cancer cells. Lycopene significantly inhibited prostate and breast cancer cell growth at physiologically relevant concentrations of ≥1.25 μM. Similar concentrations also caused a 30-40 % reduction in inhibitor of kappa B (IκB) phosphorylation in the cells, as determined by western blotting. Furthermore, the same degree of inhibition by Lycopene was observed for NF-κB transcriptional activity, as determined by reporter gene assay. Concomitant with this, immunofluorescence staining of Lycopene-treated cells showed a significant suppression (≥25 %) of TNF-induced NF-κB p65 subunit nuclear translocation. Further probing of Lycopene's effects on upstream elements of the NF-κB pathway showed a 25 % inhibition of both activity of recombinant IκB kinase β (IKKβ) kinase in a cell-free in vitro assay, as well as activity of IKKβ immunoprecipitated from MDA-MB-231 cells treated with Lycopene. In conclusion, the anticancer properties of Lycopene may occur through inhibition of the NF-κB signaling pathway, beginning at the early stage of cytoplasmic IKK kinase activity, which then leads to reduced NF-κB-responsive gene regulation. Furthermore, these effects in cancer cells were observed at concentrations of Lycopene that are relevant and achievable in vivo.
Keywords: Breast cancer; IκB kinase; Lycopene; NF-κB; Nutrition; Prostate cancer. | 2016 Aug 17;56(11):1868-79. | Lycopene and Its Antioxidant Role in the Prevention of Cardiovascular Diseases-A Critical Review[Pubmed: 25675359] | The present review is based mainly on papers published between 2000 and 2011 and gives information about the properties of the carotenoid Lycopene in chemical and biological systems and its possible role in preventing cardiovascular diseases (CVD). The main aim of this report is to highlight its role as an antioxidant, also reported are bioactive properties that may influence the development of foam cells and protection against endothelial cell damage. The paper will also examine recent observations that Lycopene may improve blood flow and reduce inflammatory responses. Lycopene possesses antioxidant properties in vitro, and some epidemiological studies have reported protective effects against the progression of CVD. The oxidation of human low density lipoproteins (LDL) is a fundamental mechanism in the initiation of atherosclerosis. A beneficial role of Lycopene as antioxidant in the prevention of CVD is suggested but the data are still controversial. Lycopene is believed to be the most potent carotenoid antioxidant in vitro. Tissue culture experiments and animal studies support potential cardioprotective effects for Lycopene and other carotenoids in the blood. Most studies showed beneficial effects of Lycopene to individuals who are antioxidant-deficient like elderly patients, or humans exposed to higher levels of oxidative stress like smokers, diabetics, hemodialysis patients and acute myocardial infarction patients. By defining the right population and combining antioxidant potentials of Lycopene with vitamins and other bioactive plant compounds, the beneficial role of Lycopene in CVD can be clarified in future studies.
Keywords: Atherosclerosis; LDL oxidation; in vitro; in vivo; isomerization. |
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In vivo: |
2017 Feb 1;263:7-17. | Lycopene inhibits reactive oxygen species production in SK-Hep-1 cells and attenuates acetaminophen-induced liver injury in C57BL/6 mice[Pubmed: 27989599] | Our aim was to investigate the antioxidant potential of Lycopene in different experimental liver models: in vitro, to evaluate the influence of Lycopene on reactive oxygen species (ROS) production mediated by the PKC pathway and in vivo, to evaluate the protective effects of Lycopene in an experimental model of hepatotoxicity. The in vitro study assessed the Lycopene antioxidant potential by the quantification of ROS production in SK-Hep-1 cells unstimulated or stimulated by an activator of the PKC pathway. The role of NADPH oxidase was evaluated by measuring its inhibition potential using an inhibitor of this enzyme. In the in vivo study, male C57BL/6 mice received Lycopene (10 or 100 mg/kg by oral gavage) and 1 h later, acetaminophen (APAP) (500 mg/kg) was administrated. Lycopene decreased ROS production in SK-Hep-1 cells through inhibition of NADPH oxidase, brought about in the PKC pathway. Lycopene improved hepatotoxicity acting as an antioxidant, reduced GSSG and regulated tGSH and CAT levels, reduced oxidative damage primarily by decreasing protein carbonylation, promoted the downregulation of MMP-2 and reduced areas of necrosis improving the general appearance of the lesion in C57BL/6 mice. Lycopene is a natural compound that was able to inhibit the production of ROS in vitro and mitigate the damage caused by APAP overdose in vivo.
Keywords: Acetaminophen; C57BL/6 mice; Hepatotoxicity; Lycopene; Oxidative stress; SK-Hep-1 cells.
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