LYCOPIN (Lycopene)
Aktuelle wissenschaftliche Studien | 131-150
131: Breast Cancer Res Treat. 2007 Aug;104(2):221-30. Epub 2006 Oct 19.
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Lycopene and other carotenoids inhibit estrogenic activity of 17beta-estradiol and genistein in cancer cells.
Hirsch K, Atzmon A, Danilenko M, Levy J, Sharoni Y.
Department of Clinical Biochemistry, Faculty of Health Sciences, Ben-Gurion University of the Negev and Soroka Medical Center of Kupat Holim, P.O. Box 653, Beer-Sheva 84105, Israel.
Epidemiological evidence suggests that carotenoids prevent several types of cancer, including mammary and endometrial cancers. On the other hand, such studies have also shown that estrogens are the most important risk factors for these cancer types. Genistein, the phytoestrogen mainly found in soy, also shows significant estrogenic activity when tested at concentrations found in human blood. The aim of this study was to determine whether carotenoids inhibit signaling of steroidal estrogen and phytoestrogen which could explain their cancer preventive activity. Similar to the known effect of 17beta-estradiol (E(2)), treatment of breast (T47D and MCF-7) and endometrial (ECC-1) cancer cells with phytoestrogens induced cell proliferation, cell-cycle progression and transactivation of the estrogen response element (ERE). However, each of the tested carotenoids (lycopene, phytoene, phytofluene, and beta-carotene) inhibited cancer cell proliferation induced by either E(2) or genistein. The inhibition of cell growth by lycopene was accompanied by slow down of cell-cycle progression from G1 to S phase. Moreover, the carotenoids inhibited estrogen-induced transactivation of ERE that was mediated by both estrogen receptors (ERs) ERalpha and ERbeta. The possibility that this inhibition results from competition of carotenoid-activated transcription systems on a limited pool of shared coactivators with the ERE transcription system was tested. Although cotransfection of breast and endometrial cancer cells with four different coactivators (SRC-1, SRC-2, SRC-3, and DRIP) strongly stimulated ERE reporter gene activity, it did not oppose the inhibitory effect of carotenoids. These results suggest that dietary carotenoids inhibit estrogen signaling of both 17beta-estradiol and genistein, and attenuate their deleterious effect in hormone-dependent malignancies.
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PMID: 17051425 [PubMed - indexed for MEDLINE]
132: Eur J Cancer Prev. 2007 Aug;16(4):298-303.
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Tomato lycopene extract supplementation decreases insulin-like growth factor-I levels in colon cancer patients.
Walfisch S, Walfisch Y, Kirilov E, Linde N, Mnitentag H, Agbaria R, Sharoni Y, Levy J.
Colorectal Unit, Faculty of Health Sciences, Ben-Gurion University of the Negev and Soroka Medical Center of Kupat Holim, Beer-Sheva, Israel.
Epidemiological studies have shown that high serum levels of insulin-like growth factor-I are associated with an increased risk of colon and other types of cancer. The aim of this study was to determine whether short intervention with dietary tomato lycopene extract will affect serum levels of the insulin-like growth factor system components in colon cancer patients. The study had a double-blind, randomized, placebo-controlled design. Colon cancer patients (n=56), candidates for colectomy, were recruited from the local community a few days to a few weeks before surgery. Personal and medical data were recorded. Plasma concentrations of insulin-like growth factor-I and II and insulin-like growth factor-I-binding protein-3 were assayed by routine laboratory methods. Lycopene was assayed by high-performance liquid chromatography. Plasma lycopene levels increased by twofold after supplementation with tomato lycopene extract. In the placebo-treated group, there was a small nonsignificant increase in lycopene plasma levels. The plasma concentration of insulin-like growth factor-I decreased significantly by about 25% after tomato lycopene extract supplementation as compared with the placebo-treated group (P<0.05). No significant change was observed in insulin-like growth factor-I-binding protein-3 or insulin-like growth factor-II, whereas the insulin-like growth factor-I/insulin-like growth factor-I-binding protein-3 molar ratio decreased significantly (P<0.05). Given that high plasma levels of insulin-like growth factor-I have been suggested as a risk factor for various types of cancer including colon cancer, the results support our suggestion that tomato lycopene extract has a role in the prevention of colon and possibly other types of cancer.
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PMID: 17554202 [PubMed - indexed for MEDLINE]
133: Eur J Clin Nutr. 2007 Aug;61(8):1011-22. Epub 2007 Feb 14.
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Influence of habitual diet on antioxidant status: a study in a population of vegetarians and omnivores.
Haldar S, Rowland IR, Barnett YA, Bradbury I, Robson PJ, Powell J, Fletcher J.
Northern Ireland Centre for Food and Health (NICHE), School of Biomedical Sciences, University of Ulster, Coleraine, County Londonderry, UK. s.haldar@ulster.ac.uk
BACKGROUND: Antioxidant status can be used as a biomarker to assess chronic disease risk and diet can modulate antioxidant defence. OBJECTIVE: To examine effects of vegetarian diet and variations in the habitual intakes of foods and nutrients on blood antioxidants. SUBJECTS AND SETTING: Thirty-one vegetarians (including six vegans) and 58 omnivores, non-smokers, in Northern Ireland. DESIGN: A diet history method was used to assess habitual diet. Antioxidant vitamins, carotenoids, uric acid, zinc- and ferric-reducing ability of plasma (FRAP) were measured in fasting plasma and activities of glutathione peroxidase (GPX), superoxide dismutase (SOD) and glutathione S-transferase (GST) and level of reduced glutathione (GSH) were measured in erythrocytes. RESULTS: Vegetarians had approximately 15% higher levels of plasma carotenoids compared with omnivores, including lutein (P< or =0.05), alpha-cryptoxanthin P< or =0.05), lycopene (NS), alpha-carotene (NS) and beta-carotene (NS). The levels/activities of all other antioxidants measured were similar between vegetarians and omnivores. Total intake of fruits, vegetables and fruit juices was positively associated with plasma levels of several carotenoids and vitamin C. Intake of vegetables was positively associated with plasma lutein, alpha-cryptoxanthin, alpha-carotene and beta-carotene, whereas intake of fruits was positively associated with plasma beta-cryptoxanthin. Intake of tea and wine was positively associated with FRAP value, whereas intake of herbal tea associated positively with plasma vitamin C. Intakes of meat and fish were positively associated with plasma uric acid and FRAP value. CONCLUSIONS: The overall antioxidant status was similar between vegetarians and omnivores. Good correlations were found between intakes of carotenoids and their respective status in blood.
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PMID: 17299498 [PubMed - indexed for MEDLINE]
134: FEBS J. 2007 Aug;274(16):4306-14. Epub 2007 Jul 27.
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Cooperation of two carotene desaturases in the production of lycopene in Myxococcus xanthus.
Iniesta AA, Cervantes M, Murillo FJ.
Departamento de Genética y Microbiología, Facultad de Biología, Universidad de Murcia, Spain. ainiesta@stanford.edu
In Myxococcus xanthus, all known carotenogenic genes are grouped together in the gene cluster carB-carA, except for one, crtIb (previously named carC). We show here that the first three genes of the carB operon, crtE, crtIa, and crtB, encode a geranygeranyl synthase, a phytoene desaturase, and a phytoene synthase, respectively. We demonstrate also that CrtIa possesses cis-to-trans isomerase activity, and is able to dehydrogenate phytoene, producing phytofluene and zeta-carotene. Unlike the majority of CrtI-type phytoene desaturases, CrtIa is unable to perform the four dehydrogenation events involved in converting phytoene to lycopene. CrtIb, on the other hand, is incapable of dehydrogenating phytoene and lacks cis-to-trans isomerase activity. However, the presence of both CrtIa and CrtIb allows the completion of the four desaturation steps that convert phytoene to lycopene. Therefore, we report a unique mechanism where two distinct CrtI-type desaturases cooperate to carry out the four desaturation steps required for lycopene formation. In addition, we show that there is a difference in substrate recognition between the two desaturases; CrtIa dehydrogenates carotenes in the cis conformation, whereas CrtIb dehydrogenates carotenes in the trans conformation.
Publication Types:
PMID: 17662111 [PubMed - indexed for MEDLINE]
135: J Am Geriatr Soc. 2007 Aug;55(8):1206-15.
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The interplay between uric acid and antioxidants in relation to physical function in older persons.
Ruggiero C, Cherubini A, Guralnik J, Semba RD, Maggio M, Ling SM, Lauretani F, Bandinelli S, Senin U, Ferrucci L.
Longitudinal Studies Section, Clinical Research Branch, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21225, USA.
OBJECTIVES: To investigate the relationship between circulating uric acid (UA) levels and plasma antioxidants and whether antioxidant levels modulate the association between UA and physical function. DESIGN: Cross-sectional. SETTING: Community-based. PARTICIPANTS: Nine hundred sixty-six elderly persons participating in the baseline assessment of the Invecchiare in Chianti Study. MEASUREMENTS: UA, carotenoid, tocopherol, and selenium concentrations were assayed. Physical function was measured using the Short Physical Performance Battery (SPPB) and difficulties in instrumental activities of daily living (IADLs). Potential confounders were assessed using standardized methods. RESULTS: Total carotenoids (P=.008), in particular alpha-carotene (P=.02), lutein (P<.001), zeaxanthin (P<.001), lycopene (P=.07), cryptoxanthin (P=.29), and selenium (P=.04) were inversely associated with UA levels. Total tocopherols (P=.06) and alpha-tocopherol (P=.10) had a positive trend across UA levels. SPPB (P=.01) and IADL disability (P=.002) were nonlinearly distributed across the UA quintiles. Participants within the middle UA quintile (4.8-5.3 mg/dL) were less disabled in IADLs and had better SPPB scores than those in the extreme UA quintiles. There was a significant interaction between UA and selenium in the model predicting SPPB score (P=.02). CONCLUSION: UA levels are inversely associated with circulating carotenoids and selenium. Participants with intermediate UA levels had a higher prevalence of good physical functions, higher SPPB scores, and lower IADL disability. This study suggests that older subjects with intermediate UA levels may have an optimum balance between proinflammatory and antioxidant compounds that may contribute to better physical performance.
Publication Types:
- Research Support, N.I.H., Extramural
- Research Support, N.I.H., Intramural
- Research Support, Non-U.S. Gov't
PMID: 17661959 [PubMed - indexed for MEDLINE]
136: J Food Sci. 2007 Aug;72(6):C307-12.
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Processing tangerine tomatoes: effects on lycopene-isomer concentrations and profile.
Ishida BK, Roberts JS, Chapman MH, Burri BJ.
Processed Foods Research Unit, Western Regional Research Center, USDA, ARS, 800 Buchanan St., Albany, CA 94710, USA. bkishida@pw.usda.gov
Because lycopene is a powerful biological antioxidant, its delivery to humans is of major concern. cis-Lycopene isomers are more bioavailable than the all-trans isomers and thus more efficiently absorbed. Tangerine tomatoes, whose lycopene isomeric content is almost all tetra-cis, provide a useful food source for comparing cis- and trans-isomer absorption. Tangerine tomatoes were processed into sauce in the Univ. of California, Davis Pilot Plant for subsequent use in a human feeding study described in another publication. Samples were taken at several stages during processing and carotenoids extracted and analyzed for carotenoid-isomer profiles and concentrations. Analyses showed that total lycopene concentration decreased considerably during the 1st step of processing, which included heating and juicing operations. Processing resulted in a large decrease in tetra-cis lycopene concentration accompanied by increases in trans- and other cis-lycopene isomers.
PMID: 17995670 [PubMed - indexed for MEDLINE]
137: Mol Nutr Food Res. 2007 Aug;51(8):956-61.
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Synergistic effects of phenolics and carotenoids on human low-density lipoprotein oxidation.
Milde J, Elstner EF, Grassmann J.
Department of Plant Sciences, Institute of Phytopathology, Laboratory for Applied Biochemistry, Munich Technical University, Freising-Weihenstephan, Germany.
Low-density lipoprotein oxidation is believed to play an important role in the development of atherosclerosis and therefore a high resistance of LDL against oxidation may prevent atherogenesis and accompanying disorders. Several secondary plant metabolites have been tested for their ability to prevent oxidation of LDL and many phenolics as well as carotenoids have been shown to enhance LDL oxidation resistance. We showed that the quercetingylcoside rutin is able to inhibit copper-induced formation of conjugated dienes and loss of tryptophan fluorescence in LDL. However, enrichment of LDL with the carotenoids lutein or lycopene did not result in an alleviation of LDL oxidation. Since there is an agreement that not one antioxidant alone can lead to health benefits but the combination, as found for example in fruits and vegetables, is the active principle, we tested whether the combination of a phenolic compound (i. e. rutin) and carotenoids (i.e. lutein or lycopene) leads to synergistic effects. Both combinations were shown to exert supra-additive protection of LDL towards oxidation, which is most likely due to different allocation of the antioxidants in the LDL-particle and to different mechanisms of antioxidant action.
PMID: 17639513 [PubMed - indexed for MEDLINE]
138: Toxicol In Vitro. 2007 Aug;21(5):840-5. Epub 2007 Jan 31.
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Lycopene activity against chemically induced DNA damage in Chinese hamster ovary cells.
Scolastici C, Alves de Lima RO, Barbisan LF, Ferreira AL, Ribeiro DA, Salvadori DM.
Department of Pathology, Botucatu Medical School, Sao Paulo State University, UNESP 18518-000, SP, Brazil.
Lycopene is a natural pigment synthesized by plants and microorganisms, and it is mainly found in tomatoes. It is an acyclic isomer of beta-carotene and one of the most potent antioxidants. Several studies have demonstrated the ability of lycopene to prevent chemically induced DNA damage; however, the mechanisms involved are still not clear. In the present study, we investigated the antigenotoxic/antimutagenic effects of lycopene in Chinese Hamster Ovary Cells (CHO) treated with hydrogen peroxide, methylmethanesulphonate (MMS), or 4-nitroquinoline-1-oxide (4-NQO). Lycopene (97%), at final concentrations of 10, 25, and 50 microM, was tested under three different protocols: before, simultaneously, and after the treatment with the mutagens. Comet and cytokinesis-block micronucleus assays were used to evaluate the level of DNA damage. Data showed that lycopene reduced the frequency of micronucleated cells induced by the three mutagens. However, this chemopreventive activity was dependent on the concentrations and treatment schedules used. Similar results were observed in the comet assay, although some enhancements of primary DNA damage were detected when the carotenoid was administered after the mutagens. In conclusion, our findings confirmed the chemopreventive activity of lycopene, and showed that this effect occurs under different mechanisms.
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PMID: 17350795 [PubMed - indexed for MEDLINE]
139: J Agric Food Chem. 2007 Jul 25;55(15):6387-94. Epub 2007 Jun 27.
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Comparative in vitro bioaccessibility of carotenoids from relevant contributors to carotenoid intake.
Granado-Lorencio F, Olmedilla-Alonso B, Herrero-Barbudo C, Pérez-Sacristan B, Blanco-Navarro I, Blazquez-García S.
Unidad de Vitaminas, Servicio de Bioquímica Clínica, Hospital Universitario Puerta de Hierro, 28035 Madrid, Spain. fgranado.hpth@salud.madrid.org
To compare the in vitro bioaccessibility of lutein, zeaxanthin, beta-cryptoxanthin, lycopene, and alpha-and beta-carotenes from relevant dietary contributors, a gastrointestinal model was used to assess the stability, isomerization, carotenol ester hydrolysis, and micellarization. Salivar, gastric, duodenal, and micellar phases were extracted, with and without saponification, and analyzed by using a quality-controlled HPLC method. The stability of carotenoids under digestion conditions was >75%, regardless of the food analyzed, whereas micellarization ranged from 5 to 100%, depending on the carotenoid and the food. cis-Isomers were maintained in processed foods, but increased in fresh foods. Xanthophyll ester hydrolysis was incomplete (<40%), and both free and ester forms were incorporated into supernatants, regardless of the xanthophyll involved and the food assessed. In vitro bioaccesibility varies widely both for different carotenoids in a given food and for a given carotenoid in different foods. Although in vitro bioaccesibility may not be enough to predict the in vivo bioavailability, it may be relevant for the food industry and for food-based dietary guidelines.
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PMID: 17595101 [PubMed - indexed for MEDLINE]
140: J Agric Food Chem. 2007 Jul 25;55(15):6285-91. Epub 2007 Jun 22.
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Mechanism of deactivation of triplet-excited riboflavin by ascorbate, carotenoids, and tocopherols in homogeneous and heterogeneous aqueous food model systems.
Cardoso DR, Olsen K, Skibsted LH.
Departamento de Química e Física Molecular, Instituto de Química de São Carlos, Universidade de São Paulo, CP 780, CEP 13560-970, São Carlos, SP, Brazil.
Tocopherols (alpha, beta, gamma, and delta) and Trolox were found to deactivate triplet-excited riboflavin in homogeneous aqueous solution (7:3 v/v tert-butanol/water) with second-order reaction rates close to diffusion control [k2 between 4.8 x 10(8) (delta-tocopherol) and 6.2 x 10(8) L mol(-1) s(-1) (Trolox) at 24.0 +/- 0.2 degrees C] as determined by laser flash photolysis transient absorption spectroscopy. In aqueous buffer (pH 6.4) the rate constant for Trolox was 2.6 x 10(9) L mol(-1) s1 and comparable to the rate constant found for ascorbate (2.0 x 10(9) L mol(-1) s(-1)). The deactivation rate constant was found to be inferior in heterogeneous systems as shown for alpha-tocopherol and Trolox in aqueous Tween-20 emulsion (approximately by a factor of 4 compared to 7:3 v/v tert-butanol/water). Neither beta-carotene (7:3 v/v tert-butanol/water and Tween-20 emulsion), lycopene (7:3 v/v tert-butanol/water), nor crocin (aqueous buffer at pH 6.4, 7:3 v/v tert-butanol/water, and Tween-20 emulsion) showed any quenching on the triplet excited state of riboflavin. Therefore, all carotenoids seem to reduce the formation of triplet-excited riboflavin through an inner-filter effect. Activation parameters were based on the temperature dependence of the triplet-excited deactivation between 15 and 35 degrees C, and the isokinetic behavior, which was found to include purine derivatives previously studied, confirms a common deactivation mechanism with a bimolecular diffusion-controlled encounter with electron (or hydrogen atom) transfer as rate-determining step. DeltaH for deactivation by ascorbic acid, Trolox, and homologue tocopherols (ranging from 18 kJ mol(-1) for Trolox in Tween-20 emulsion to 184 kJ mol(-1) for ascorbic acid in aqueous buffer at pH 6.4) showed a linear dependence on DeltaS (ranging from -19 J mol(-1) K(-1) for Trolox in aqueous buffer at pH 6.4 to +550 J mol(-1) K(-1) for ascorbic acid in aqueous buffer pH 6.4). Among photooxidation products from the chemical quenching, lumicrome, alpha-tocopherol quinones and epoxyquinones, and alpha-tocopherol dimers were identified by ESI-QqTOF-MS.
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PMID: 17585774 [PubMed - indexed for MEDLINE]
141: J Natl Cancer Inst. 2007 Jul 18;99(14):1074-85. Epub 2007 Jul 10.
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Comment in:
The U.S. Food and Drug Administration's evidence-based review for qualified health claims: tomatoes, lycopene, and cancer.
Kavanaugh CJ, Trumbo PR, Ellwood KC.
RD, Center for Food Safety and Applied Nutrition, U.S. Food and Drug Administration, HFS-830, 5100 Paint Branch Parkway, College Park, MD 20740, USA. claudine.kavanaugh@fda.hhs.gov
Several studies have reported an inverse association between tomato and/or lycopene intake and the risk of some types of cancer. In 2004, the U.S. Food and Drug Administration (FDA) received two petitions for qualified health claims regarding tomatoes, lycopene, and the risk reduction for some forms of cancer. Health claims that characterize the relationship between a food or food component and a disease or health-related condition require premarket approval by FDA to be included on the labels of conventional foods and dietary supplements. Here we describe FDA's review of the scientific data for tomato and/or lycopene intake with respect to risk reduction for certain forms of cancer. The FDA found no credible evidence to support an association between lycopene intake and a reduced risk of prostate, lung, colorectal, gastric, breast, ovarian, endometrial, or pancreatic cancer. The FDA also found no credible evidence for an association between tomato consumption and a reduced risk of lung, colorectal, breast, cervical, or endometrial cancer. The FDA found very limited evidence to support an association between tomato consumption and reduced risks of prostate, ovarian, gastric, and pancreatic cancers.
Publication Types:
PMID: 17623802 [PubMed - indexed for MEDLINE]
142: J Natl Cancer Inst. 2007 Jul 18;99(14):1060-2. Epub 2007 Jul 10.
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Comment on:
Does prostate-specific antigen screening influence the results of studies of tomatoes, lycopene, and prostate cancer risk?
Giovannucci E.
Publication Types:
PMID: 17623795 [PubMed - indexed for MEDLINE]
143: J Natl Cancer Inst. 2007 Jul 18;99(14):1059. Epub 2007 Jul 10.
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Comment on:
Evidence-based reviews in support of health policy decisions.
Coates PM.
Publication Types:
PMID: 17623794 [PubMed - indexed for MEDLINE]
144: Mutat Res. 2007 Jul 10;631(1):26-35. Epub 2007 Apr 7.
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Tomato-oleoresin supplement prevents doxorubicin-induced cardiac myocyte oxidative DNA damage in rats.
Ferreira AL, Salvadori DM, Nascimento MC, Rocha NS, Correa CR, Pereira EJ, Matsubara LS, Matsubara BB, Ladeira MS.
Department of Internal Medicine, Botucatu Faculty of Medicine, UNESP, São Paulo State University, Botucatu, Brazil. ferreira@fmb.unesp.br
Doxorubicin (DOX) is an efficient chemotherapeutic agent used against several types of tumors; however, its use is limited due to severe cardiotoxicity. Since it is accepted that reactive oxygen species are involved in DOX-induced cardiotoxicity, antioxidant agents have been used to attenuate its side effects. To determine tomato-oleoresin protection against cardiac oxidative DNA damage induced by DOX, we distributed Wistar male rats in control (C), lycopene (L), DOX (D) and DOX+lycopene (DL) groups. They received corn oil (C, D) or tomato-oleoresin (5mg/kg body wt. day) (L, DL) by gavage for a 7-week period. They also received saline (C, L) or DOX (4mg/kg body wt.) (D, DL) intraperitoneally at the 3rd, 4th, 5th, and at 6th week. Lycopene absorption was checked by HPLC. Cardiac oxidative DNA damage was evaluated by the alkaline Comet assay using formamidopyrimidine-DNA glycosylase (FPG) and endonuclease III (endo III). Cardiomyocyte levels of SBs, SBs FPG and SBs Endo III were higher in rats from D when compared to other groups. DNA damage levels in cardiomyocytes from DL were not different when compared to C and L groups. The viability of cardiomyocytes from D or DL was lower than C or L groups (p<0.01). Lycopene levels (mean+/-S.D.nmol/kg) in saponified hearts were similar between L (47.43+/-11.78) and DL (49.85+/-16.24) groups. Our results showed: (1) lycopene absorption was confirmed by its cardiac levels; (2) DOX-induced oxidative DNA damage in cardiomyocyte; (3) tomato-oleoresin supplementation protected against cardiomyocyte oxidative DNA damage.
Publication Types:
PMID: 17499013 [PubMed - indexed for MEDLINE]
145: Proc Natl Acad Sci U S A. 2007 Jul 10;104(28):11784-9. Epub 2007 Jul 2.
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Identification of a fourth family of lycopene cyclases in photosynthetic bacteria.
Maresca JA, Graham JE, Wu M, Eisen JA, Bryant DA.
Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA 16802, USA.
A fourth and large family of lycopene cyclases was identified in photosynthetic prokaryotes. The first member of this family, encoded by the cruA gene of the green sulfur bacterium Chlorobium tepidum, was identified in a complementation assay with a lycopene-producing strain of Escherichia coli. Orthologs of cruA are found in all available green sulfur bacterial genomes and in all cyanobacterial genomes that lack genes encoding CrtL- or CrtY-type lycopene cyclases. The cyanobacterium Synechococcus sp. PCC 7002 has two homologs of CruA, denoted CruA and CruP, and both were shown to have lycopene cyclase activity. Although all characterized lycopene cyclases in plants are CrtL-type proteins, genes orthologous to cruP also occur in plant genomes. The CruA- and CruP-type carotenoid cyclases are members of the FixC dehydrogenase superfamily and are distantly related to CrtL- and CrtY-type lycopene cyclases. Identification of these cyclases fills a major gap in the carotenoid biosynthetic pathways of green sulfur bacteria and cyanobacteria.
Publication Types:
PMID: 17606904 [PubMed - indexed for MEDLINE]
PMCID: PMC1905924
146: Eur J Pharmacol. 2007 Jul 2;566(1-3):192-9. Epub 2007 Apr 6.
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Lycopene, quercetin and tyrosol prevent macrophage activation induced by gliadin and IFN-gamma.
De Stefano D, Maiuri MC, Simeon V, Grassia G, Soscia A, Cinelli MP, Carnuccio R.
Dipartimento di Farmacologia Sperimentale, Via D. Montesano, 49, Università degli Studi di Napoli Federico II, 80131 Naples, Italy. dadestef@unina.it
Oxidative stress plays an important role in inflammatory process of celiac disease. We have studied the effect of the lycopene, quercetin and tyrosol natural antioxidants on the inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) gene expression in RAW 264.7 macrophages stimulated by gliadin in association with IFN-gamma. The IFN-gamma plus gliadin combination treatment was capable of enhancing iNOS and COX-2 gene expression and nuclear factor-kappaB (NF-kappaB), interferon regulatory factor-1 (IRF-1) and signal transducer and activator of transcription-1alpha (STAT-1alpha) activation induced by reactive oxygen species generation at 24 h. Lycopene, quercetin and tyrosol inhibited all these effects. The results here reported suggest that these compounds may represent non toxic agents for the control of pro-inflammatory genes involved in celiac disease.
PMID: 17477920 [PubMed - indexed for MEDLINE]
147: Appl Environ Microbiol. 2007 Jul;73(13):4342-50. Epub 2007 May 11.
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High-level production of beta-carotene in Saccharomyces cerevisiae by successive transformation with carotenogenic genes from Xanthophyllomyces dendrorhous.
Verwaal R, Wang J, Meijnen JP, Visser H, Sandmann G, van den Berg JA, van Ooyen AJ.
Fungal Genomics, Laboratory of Microbiology, Wageningen University, Dreijenlaan 2, Wageningen, The Netherlands.
To determine whether Saccharomyces cerevisiae can serve as a host for efficient carotenoid and especially beta-carotene production, carotenogenic genes from the carotenoid-producing yeast Xanthophyllomyces dendrorhous were introduced and overexpressed in S. cerevisiae. Because overexpression of these genes from an episomal expression vector resulted in unstable strains, the genes were integrated into genomic DNA to yield stable, carotenoid-producing S. cerevisiae cells. Furthermore, carotenoid production levels were higher in strains containing integrated carotenogenic genes. Overexpression of crtYB (which encodes a bifunctional phytoene synthase and lycopene cyclase) and crtI (phytoene desaturase) from X. dendrorhous was sufficient to enable carotenoid production. Carotenoid production levels were increased by additional overexpression of a homologous geranylgeranyl diphosphate (GGPP) synthase from S. cerevisiae that is encoded by BTS1. Combined overexpression of crtE (heterologous GGPP synthase) from X. dendrorhous with crtYB and crtI and introduction of an additional copy of a truncated 3-hydroxy-3-methylglutaryl-coenzyme A reductase gene (tHMG1) into carotenoid-producing cells resulted in a successive increase in carotenoid production levels. The strains mentioned produced high levels of intermediates of the carotenogenic pathway and comparable low levels of the preferred end product beta-carotene, as determined by high-performance liquid chromatography. We finally succeeded in constructing an S. cerevisiae strain capable of producing high levels of beta-carotene, up to 5.9 mg/g (dry weight), which was accomplished by the introduction of an additional copy of crtI and tHMG1 into carotenoid-producing yeast cells. This transformant is promising for further development toward the biotechnological production of beta-carotene by S. cerevisiae.
Publication Types:
PMID: 17496128 [PubMed - indexed for MEDLINE]
PMCID: PMC1932764
148: Basic Clin Pharmacol Toxicol. 2007 Jul;101(1):16-24.
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Effect of lycopene on doxorubicin-induced cardiotoxicity: an echocardiographic, histological and morphometrical assessment.
Anjos Ferreira AL, Russell RM, Rocha N, Placido Ladeira MS, Favero Salvadori DM, Oliveira Nascimento MC, Matsui M, Carvalho FA, Tang G, Matsubara LS, Matsubara BB.
Department of Internal Medicine, Botucatu Faculty of Medicine, Universidade Estadual Paulista, São Paulo State University, Botucatu, SP, Brazil. ferreira@fmb.unesp.br
Doxorubicin is an excellent chemotherapeutic agent utilized for several types of cancer but the irreversible doxorubicin-induced cardiac damage is the major limitation for its use. Oxidative stress seems to be associated with some phase of the toxicity mechanism process. To determine if lycopene protects against doxorubicin-induced cardiotoxicity, male Wistar rats were randomly assigned either to control, lycopene, doxorubicin or doxorubicin + lycopene groups. They received corn oil (control, doxorubicin) or lycopene (5 mg/kg body weight a day) (lycopene, doxorubicin + lycopene) by gavage for a 7-week period. They also received saline (control, lycopene) or doxorubicin (4 mg/kg) (doxorubicin, doxorubin + lycopene) intraperitoneally by week 3, 4, 5 and 6. Animals underwent echocardiogram and were killed for tissue analyses by week 7. Mean lycopene levels (nmol/kg) in liver were higher in the doxorubicin + lycopene group (5822.59) than in the lycopene group (2496.73), but no differences in lycopene were found in heart or plasma of these two groups. Lycopene did not prevent left ventricular systolic dysfunction induced by doxorubicin. However, morphologic examination revealed that doxorubicin-induced myocyte damage was significantly suppressed in rats treated with lycopene. Doxorubicin treatment was followed by increase of myocardium interstitial collagen volume fraction. Our results show that: (i) doxorubicin-induced cardiotoxicity was confirmed by echocardiogram and morphological evaluations; (ii) lycopene absorption was confirmed by its levels in heart, liver and plasma; (iii) lycopene supplementation provided myocyte protection without preventing interstitial collagen accumulation increase; (iv) doxorubicin-induced cardiac dysfunction was not prevented by lycopene supplementation; and (v) lycopene depletion was not observed in plasma and tissues from animals treated with doxorubicin.
Publication Types:
PMID: 17577311 [PubMed - indexed for MEDLINE]
149: Biomed Pharmacother. 2007 Jul;61(6):366-9. Epub 2007 Mar 19.
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Lycopene affects proliferation and apoptosis of four malignant cell lines.
Salman H, Bergman M, Djaldetti M, Bessler H.
Department of Medicine C, Rabin Medical Center-Golda Campus (Hasharon), Petah-Tiqva, and the Sackler School of Medicine, Tel-Aviv University, Ramat-Aviv, Israel.
The beneficial effect of lycopene from tomatoes on a variety of chronic diseases and particularly its association with decreased incidence of prostate and breast cancer seems to be well established. The aim of the study was to examine its anti-proliferative and apoptotic effect on other malignant cell lines. Cells of the following lines were incubated with 1.0, 2.0, and 4.0microM of lycopene: human colon carcinoma (HuCC), B chronic lymphocytic leukemia (EHEB), human erythroleukemia (K562) and Raji, a prototype of Burkitt lymphoma cell line. The results showed that lycopene exerted a significant dose-dependent effect on the proliferation capacity of K562, Raji and HuCC lines, whereas this effect was observed in EHEB cells only with the highest dose used in the study. Increased apoptotic rate was found after incubation of HuCC cells with 2.0 and 4.0microM of lycopene and in Raji cells following incubation with 2.0microM. The findings point out that the anti-proliferative effect of lycopene on tumor cells and its effect on the apoptotic rate depends on its dosage and on the type of the malignant cells.
PMID: 17448625 [PubMed - indexed for MEDLINE]
150: Br J Nutr. 2007 Jul;98(1):38-44. Epub 2007 Apr 20.
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Comparison of the uptake and secretion of carotene and xanthophyll carotenoids by Caco-2 intestinal cells.
O'Sullivan L, Ryan L, O'Brien N.
Department of Food and Nutritional Sciences, University College Cork, Ireland.
Carotenoids have been shown to have potential beneficial effects on human health which has led to an increasing interest in the study of their bioavailability. A Caco-2 cell model, as previously described, was employed to examine the percentage transfer of the carotenoids alpha-carotene, beta-carotene, lycopene, astaxanthin, beta-cryptoxanthin, lutein and zeaxanthin through an intact, highly differentiated Caco-2 cell monolayer at a range of different amounts. Our results show that astaxanthin, a carotenoid with powerful antioxidant capacity, had the highest percentage transfer overall. We examined the cellular uptake and secretion of lutein and zeaxanthin to compare two structurally similar carotenoids. Both were efficiently transported through the monolayer with a range between 5.1 (sem 1.2) % to 20.2 (sem 3.3) % and 5.5 (sem 2.5) % to 13.4 (sem 4) % for lutein and zeaxanthin, respectively. These carotenoids were compared to each other at each added amount and no significant difference was observed between the two xanthophylls. The carotene carotenoids alpha-carotene, beta-carotene and lycopene and the xanthophyll beta-cryptoxanthin were also examined and had lower uptake and secretion values when compared to lutein, zeaxanthin and astaxanthin. The xanthophyll beta-cryptoxanthin was also not significantly different when compared to the carotene carotenoids. Data generated from this study compares well with in vivo bioavailability studies. Furthermore, the model provides comparative data on the relative absorption and transfer of seven different carotenoids. Our data indicate that lower amounts of carotenoids were absorbed and transferred more efficiently than higher amounts suggesting a saturation effect at higher exposure.
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PMID: 17445346 [PubMed - indexed for MEDLINE]
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