Institut für Mangostan & natürliche Antioxidantien

LYCOPIN (Lycopene)

Aktuelle wissenschaftliche Studien | 171-200

171: J Cancer Res Clin Oncol. 2007 Jun;133(6):351-9. Epub 2007 Jan 12.
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Effect of lycopene on insulin-like growth factor-I, IGF binding protein-3 and IGF type-I receptor in prostate cancer cells.

Kanagaraj P, Vijayababu MR, Ravisankar B, Anbalagan J, Aruldhas MM, Arunakaran J.

Department of Endocrinology, Dr. ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani, Chennai 600113, India.

PURPOSE: Prostate cancer is the second most common cancer that leads to death in elderly men. The risk of prostate cancer prevalence is often associated with the elevated level of insulin-like growth factor-I (IGF-I) and decreased level of IGF-binding protein 3 (IGFBP-3). Lycopene, a carotenoid, reduces the proliferation of cancer cells and induces apoptosis. Hence, higher intake of lycopene can be associated with the lower risk of prostate cancer. However, the mechanism of action of lycopene in the prevention of prostate cancer is still unclear. The present study was carried out to study the effects of lycopene on the components of IGF system and apoptosis in androgen-independent prostate cancer cells (PC-3 cells). METHODS: PC-3 cells were treated with various concentrations of lycopene, (20, 40 and 60 microM) for 24, 48, 72 and 96 h. IGF-I, IGFBP-3 and IGF-I receptor (IGF-IR) levels in lycopene-treated cells were evaluated. Annexin V and propidium iodide (PI) binding studies were done to assess apoptosis. RESULTS: PC-3 cells treated with lycopene showed a significant decrease in cell proliferation. Lycopene, at a dose of 40 microM, significantly increased the level of IGFBP-3. Lycopene-induced apoptosis was confirmed by annexin V and PI binding. Lycopene-induced DNA fragmentation was absent after 24 h treatment whereas the same was observed after 48 h treatment. There was a significant decrease in the IGF-IR expression after the cells were treated with lycopene and IGF-I. CONCLUSION: The data obtained suggest that the components of the IGF system may act as a positive regulator of lycopene-induced apoptosis in PC-3 cells. Thus, the observed lycopene-induced biological effects and their associated mechanisms are encouraging and may lead to the development of a highly successful drug for the treatment of prostate cancer.

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PMID: 17219202 [PubMed - indexed for MEDLINE]


172: J Nutr. 2007 Jun;137(6):1395-400.
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Beta-carotene from red carrot maintains vitamin A status, but lycopene bioavailability is lower relative to tomato paste in Mongolian gerbils.

Mills JP, Simon PW, Tanumihardjo SA.

Interdepartmental Graduate Program in Nutritional Sciences and USDA Agricultural Research Service, Vegetable Crops Research Unit, University of Wisconsin, Madison, WI 53706, USA.

Red carrots contain lycopene in addition to alpha- and beta-carotene. The utility of red carrot as a functional food depends in part on the bioavailability of its constituent carotenoids. Lycopene bioavailability was compared in Mongolian gerbils (Meriones unguiculatus) fed freeze-dried red carrot and tomato paste (Study 1, n = 47) and whole food extracts dissolved in cottonseed oil (Study 2, n = 39). Diets and supplements were equalized for lycopene and intakes did not differ. Both studies utilized negative (oil) and positive [purified lycopene (Lyc)] controls. In Study 1, vitamin A liver stores (0.68 +/- 0.13 micromol/liver) of the red carrot group did not differ from baseline (0.63 +/- 0.13 micromol/liver) and were greater than those of the tomato paste (0.43 +/- 0.12 micromol/liver), Lyc (0.51 +/- 0.14 micromol/liver), and control (0.38 +/- 0.17 micromol/liver) groups (P < 0.003). A similar pattern was observed in Study 2. In both studies, hepatic lycopene was higher in the tomato paste (82.7 +/- 26.7 and 80.7 +/- 20.2 nmol/liver) groups compared with red carrot groups (59.3 +/- 21.9 and 39.5 +/- 14.1 nmol/liver, P < 0.0001). Hepatic lycopene from tomato paste was higher than Lyc in Study 1, but tomato paste extract and Lyc did not differ in Study 2, when both were dissolved in oil. Red carrot maintains vitamin A status, but constituent beta-carotene may interfere with lycopene bioavailability. These results confirm prior studies in humans on the relative bioavailability of lycopene from red carrots and tomato paste and expand them by suggesting the mechanism and determining vitamin A value.

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PMID: 17513397 [PubMed - indexed for MEDLINE]


173: J Nutr Sci Vitaminol (Tokyo). 2007 Jun;53(3):207-12.
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Measurement of individual differences in intake of green and yellow vegetables and carotenoids in young unmarried subjects.

Hosotani K, Kitagawa M.

Faculty of Education, Wakayama University, Wakayama 640-8510, Japan. hosotani@center.wakayama-u.ac.jp

In this study, a dietary survey for 3 weekdays of young unmarried subjects [workers and students, 159 males and 160 females, ages 18-19y (17.2%), 20-24 y (56.2%), 25-29 y (18.6%), 30-34 y (6.7%) and 35 y- (1.3%)] was performed. We evaluated the intake of green and yellow vegetables in this survey and determined the carotenoids (beta-carotene, alpha-carotene, lycopene, beta-cryptoxanthin, and lutein+zeaxanthin) in 15 kinds of green and yellow vegetables frequently consumed. The carotenoid intake of each subject was calculated from the intake of these vegetables and the amount of carotenoid. Moreover, we studied the intake of protein, fat, and dietary fiber, and investigated its relationship to the intake of vegetables. The mean green and yellow vegetable intake/d in all subjects was 60.5 +/- 58.7 g, much lower than the recommended level [120 g/d, (Health Japan 21 by Japanese Ministry of Health, Labour and Welfare)]. The intake of green and yellow vegetables was greater in females than males, and in workers than students. In all subjects, the mean total carotenoid intake/d was 2852.8 +/- 2354.3 microg. In the total intake of carotenoids, there was no difference between males and females; however, the intake was greater in workers than in students. The intake of beta-carotene and a-carotene was greater in males than females. However, the intake of beta-cryptoxanthin, lycopene, and lutein+zeaxanthin was greater in females than males. The group with the low green and yellow vegetable intake had not only a low carotenoid intake, but also a low intake of protein, fat, and dietary fiber. Therefore, it was suggested that carotenoid absorption may be affected by a low intake of protein, fat, and dietary fiber.

PMID: 17874824 [PubMed - indexed for MEDLINE]


174: Plant Physiol. 2007 Jun;144(2):1181-9. Epub 2007 Apr 13.
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Maize Y9 encodes a product essential for 15-cis-zeta-carotene isomerization.

Li F, Murillo C, Wurtzel ET.

Department of Biological Sciences, Lehman College, City University of New York, Bronx, New York 10468, USA.

Carotenoids are a diverse group of pigments found in plants, fungi, and bacteria. They serve essential functions in plants and provide health benefits for humans and animals. In plants, it was thought that conversion of the C40 carotenoid backbone, 15-cis-phytoene, to all-trans-lycopene, the geometrical isomer required by downstream enzymes, required two desaturases (phytoene desaturase and zeta-carotene desaturase [ZDS]) plus a carotene isomerase (CRTISO), in addition to light-mediated photoisomerization of the 15-cis-double bond; bacteria employ only a single enzyme, CRTI. Characterization of the maize (Zea mays) pale yellow9 (y9) locus has brought to light a new isomerase required in plant carotenoid biosynthesis. We report that maize Y9 encodes a factor required for isomerase activity upstream of CRTISO, which we term Z-ISO, an activity that catalyzes the cis- to trans-conversion of the 15-cis-bond in 9,15,9'-tri-cis-zeta-carotene, the product of phytoene desaturase, to form 9,9'-di-cis-zeta-carotene, the substrate of ZDS. We show that recessive y9 alleles condition accumulation of 9,15,9'-tri-cis-zeta-carotene in dark tissues, such as roots and etiolated leaves, in contrast to accumulation of 9,9'-di-cis-zeta-carotene in a ZDS mutant, viviparous9. We also identify a locus in Euglena gracilis, which is similarly required for Z-ISO activity. These data, taken together with the geometrical isomer substrate requirement of ZDS in evolutionarily distant plants, suggest that Z-ISO activity is not unique to maize, but will be found in all higher plants. Further analysis of this new gene-controlled step is critical to understanding regulation of this essential biosynthetic pathway.

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PMID: 17434985 [PubMed - indexed for MEDLINE]
PMCID: PMC1914175


175: Eur J Clin Nutr. 2007 May 30. [Epub ahead of print]
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Relative validity of a food frequency questionnaire used in the Inter99 study.

Toft U, Kristoffersen L, Ladelund S, Bysted A, Jakobsen J, Lau C, Jørgensen T, Borch-Johnsen K, Ovesen L.

1Research Centre for Prevention and Health, Glostrup University Hospital, Glostrup, Denmark.

Objective:To evaluate the validity of the Inter99 food frequency questionnaire (FFQ) compared with a 28-days' diet history and biomarkers.Subjects:A random sample of 13 016 individuals were drawn from a general population and invited for a health screening programme. Participation rate was 52.5%. All high-risk individuals were re-invited for assessment after 1 and 3 years and completed a 198-item FFQ at all three occasions. Participants attending for 3 years follow-up were invited to participate in the validation study, including a 28-days' diet history, a 24-h urine collection and a fasting blood sample. Overall, 264 subjects participated.Results:Spearman's rank correlation coefficients between the two dietary methods ranged from 0.31(beta-carotene) to 0.64 (fruits) in men and from 0.31 (polyunsaturated fat and sodium) to 0.64 (fruits) for women. The proportion of individuals classified in the same or adjacent quintiles were, on average, 72% for men and 69% for women. Gross misclassification was found on average in 2%. The correlation coefficients of the residuals ranged from 0.27 (sodium) to 0.61 (fruits) for men and from 0.21 (sodium) to 0.62 (B12-vitamin) for women. Correlation coefficients between fruit and vegetable intake and carotenoids ranged from -0.08 (lycopene) to 0.44 (alpha-carotene). For the residuals the correlation coefficients ranged from -0.004 (lycopene) to 0.47 (alpha-carotene).Conclusion:The Inter99 FFQ and the residuals of the intake provide acceptable classification of individuals according to their dietary intakes and the FFQ gives a good quantitative measurement of key dietary components.European Journal of Clinical Nutrition advance online publication, 30 May 2007; doi:10.1038/sj.ejcn.1602815.

PMID: 17538538 [PubMed - as supplied by publisher]


176: J Agric Food Chem. 2007 May 30;55(11):4474-80. Epub 2007 May 3.
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Organic vs conventionally grown Rio Red whole grapefruit and juice: comparison of production inputs, market quality, consumer acceptance, and human health-bioactive compounds.

Lester GE, Manthey JA, Buslig BS.

Kika de la Garza Subtropical Agricultural Research Center, Agricultural Research Service, U.S. Department of Agriculture, Weslaco, Texas 78596, USA. glester@weslaco.ars.usda.gov

Most claims that organic produce is better tasting and more nutritious than nonorganic (conventional) produce are largely unsubstantiated. This is due mainly to a lack of rigor in research studies matching common production variables of both production systems, such as microclimate, soil type, fertilizer elemental concentration, previous crop, irrigation source and application, plant age, and cultivar. The aforementioned production variables common to both production systems were matched for comparison of Texas commercially grown conventional and certified organic Rio Red red-fruited grapefruit. Whole grapefruits from each production system were harvested between 800 and 1000 h at commercial early (November), mid- (January), and late season (March) harvest periods for three consecutive years. Within each harvest season, conventional and organic whole fruits were compared for marketable qualities (fruit weight, specific gravity, peel thickness, and peel color), and juices were compared for marketable qualities (specific gravity, % juice, and color), human health-bioactive compounds (minerals, ascorbic acid, lycopene, sugars, pectin, phenols, and nitrates), and consumer taste intensity and overall acceptance. Conventional fruit was better colored and higher in lycopene, and the juice was less tart, lower in the bitter principle naringin, and better accepted by the consumer panel than the organic fruit. Organic fruit had a commercially preferred thinner peel, and the juice was higher in ascorbic acid and sugars and lower in nitrate and the drug interactive furanocoumarins.

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PMID: 17474757 [PubMed - indexed for MEDLINE]


177: Arch Biochem Biophys. 2007 May 15;461(2):235-41. Epub 2007 Mar 21.
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Kinetic variations determine the product pattern of phytoene desaturase from Rubrivivax gelatinosus.

Stickforth P, Sandmann G.

Molecular Biosciences 213, J.W. Goethe Universität, P.O. Box 111932, D-60054 Frankfurt, Germany.

In bacteria and fungi, the degree of carotenoid desaturation is determined by a single enzyme, the CrtI-type phytoene desaturase. In different organisms, this enzyme can carry out either three, four or even five desaturation steps. The purple bacterium Rubrivivax gelatinosus is the only known species in which reaction products of a 3-step and a 4-step desaturation (i.e. neurosporene and lycopene derivatives) accumulate simultaneously. The properties of this phytoene desaturation to catalyze neurosporene or lycopene were analyzed by heterologous complementations in Escherichia coli and by in vitro studies. They demonstrated that high enzyme concentrations or low phytoene supply favor the formation of lycopene. Under these conditions, CrtI from Rhodobacter spheroides can be forced in vitro to lycopene formation although this carotene is not synthesized in this species. All results can be explained by a model based on the competition between phytoene and neurosporene for the substrate binding site of phytoene desaturase. Mutations in CrtI from Rvi. gelatinosus have been generated resulting in increased lycopene formation in Escherichia coli. This modification in catalysis is due to increased amounts of CrtI protein.

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PMID: 17428435 [PubMed - indexed for MEDLINE]


178: J Agric Food Chem. 2007 May 2;55(9):3414-20. Epub 2007 Mar 31.
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Carotenoid accumulation in Japanese apricot (Prunus mume Siebold & Zucc.): molecular analysis of carotenogenic gene expression and ethylene regulation.

Kita M, Kato M, Ban Y, Honda C, Yaegaki H, Ikoma Y, Moriguchi T.

National Institute of Fruit Tree Science, Tsukuba, Ibaraki 305-8605, Japan. mkita@affrc.go.jp

To elucidate the regulatory mechanisms of carotenogenesis in Japanese apricot (Prunus mume Siebold & Zucc.), the relationships between carotenoid accumulation and the expression of the carotenogenic genes, phytoene synthase (PmPSY-1), phytoene desaturase (PmPDS), zeta-carotene desaturase (PmZDS), lycopene beta-cyclase (PmLCYb), lycopene epsilon-cyclase (PmLCYe), beta-carotene hydroxylase (PmHYb), and zeaxanthin epoxidase (PmZEP), were analyzed in two cultivars with different ripening traits, 'Orihime' and 'Nanko.' In 'Orihime' fruits, large amounts of carotenoids accumulated on the tree, concomitant with the induction of PmPSY-1 and the downstream carotenogenic genes PmLCYb, PmHYb, and PmZEP. In 'Nanko' fruits, carotenoids accumulated mainly after harvest, correlating with an appreciable induction of PmPSY-1 expression, but the downstream genes were not notably induced, which may explain the lower total carotenoid content in 'Nanko' than in 'Orihime.' In both cultivars, a decrease in PmLCYe expression and increased or constant PmLCYb expression could cause the metabolic shift from beta,epsilon-carotenoid synthesis to beta,beta-carotenoid synthesis that occurs as ripening approaches. Next, the effects of ethylene on the expression of PmPSY-1 and carotenoid accumulation were investigated in 'Nanko' fruits treated with propylene or 1-methylcyclopropene (1-MCP). Propylene treatment induced both ethylene production and carotenoid accumulation. PmPSY-1 was constitutively expressed, but propylene treatment accelerated its induction. 1-MCP treatment caused a slight inhibition of carotenoid accumulation along with the repression, although not complete, of PmPSY-1. Collectively, although PmPSY-1 expression was not exclusively regulated by ethylene, both the notable induction of PmPSY-1 accelerated by ethylene and the subsequent induction of the downstream carotenogenic genes, especially PmLCYb, could be necessary for the massive carotenoid accumulation that occurs during ripening. Furthermore, the switch from PmLCYe expression to PmLCYb expression could cause beta,beta-carotenoid accumulation in both Japanese apricot cultivars.

PMID: 17397180 [PubMed - indexed for MEDLINE]


179: Biotechnol Adv. 2007 May-Jun;25(3):211-22. Epub 2006 Dec 19.
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Progress on molecular breeding and metabolic engineering of biosynthesis pathways of C(30), C(35), C(40), C(45), C(50) carotenoids.

Wang F, Jiang JG, Chen Q.

College of Food and Bioengineering, South China University of Technology, Guangzhou, PR China.

At least 700 natural carotenoids have been characterized; they can be classified into C(30), C(40) and C(50) subfamilies. The first step of C(40) pathway is the combination of two molecules of geranylgeranyl pyrophosphate to synthesize phytoene by phytoene synthase (CrtB or PSY). Most natural carotenoids originate from different types and levels of desaturation by phytoene desaturase (CrtI or PDS+ZDS), cyclization by lycopene cyclase (CrtY or LYC) and other modifications by different modifying enzyme (CrtA, CrtU, CrtZ or BCH, CrtX, CrtO, etc.) of this C(40) backbone. The first step of C(30) pathway is the combination of two molecules of FDP to synthesize diapophytoene by diapophytoene synthase (CrtM). But natural C(30) pathway only goes through a few steps of desaturation to form diaponeurosporene by diapophytoene desaturase (CrtN). Natural C(50) carotenoid decaprenoxanthin is synthesized starting from the C(40) carotenoid lycopene by the addition of 2 C(5) units. Concerned the importance of carotenoids, more and more attention has been concentrated on achieving novel carotenoids. The method being used successfully is to construct carotenoids biosynthesis pathways by metabolic engineering. The strategy of metabolic engineering is to engineer a small number of stringent upstream enzymes (CrtB, CrtI, CrtY, CrtM, or CrtN), then use a lot of promiscuous downstream enzymes to obtain large number of novel carotenoids. Two key enzymes phytoene desaturase (CrtI(m)) and lycopene cyclase (CrtY(m)) have been modified and used with a series of downstream modifying enzymes with broad substrate specificity, such as monooxygenase (CrtA), carotene desaturase (CrtU), carotene hydroxylase (CrtZ), zeaxanthin glycosylase (CrtX) and carotene ketolase (CrtO) to extend successfully natural C(30) and C(40) pathways in E. coli. Existing C(30) synthase CrtM to synthesize carotenoids with different chain length have been engineered and a series of novel carotenoids have been achieved using downstream modifying enzymes. C(35) carotenoid biosynthesis pathway has been constructed in E. coli as described. C(45) and C(50) carotenoid biosynthesis pathways have also been constructed in E. coli, but it is still necessary to extend these two pathways. Those novel acyclic or cyclic carotenoids have a potential ability to protect against photooxidation and radical-mediated peroxidation reactions which makes them interesting pharmaceutical candidates.

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PMID: 17257797 [PubMed - indexed for MEDLINE]


180: Biotechnol Prog. 2007 May-Jun;23(3):599-605. Epub 2007 May 15.
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Increased beta-carotene production in recombinant Escherichia coli harboring an engineered isoprenoid precursor pathway with mevalonate addition.

Yoon SH, Park HM, Kim JE, Lee SH, Choi MS, Kim JY, Oh DK, Keasling JD, Kim SW.

Division of Applied Life Science (BK21), EB-NCRC and PMBBRC, and Division of Forest Science, Gyeongsang National University, Jinju 660-701, Korea.

When pT-LYCm4 containing lycopene synthetic genes was co-transformed with pSUcrtY or pSHcrtY containing crtY gene of Pantoea ananatis (P. ananatis) or Pantoea agglomerans (P. agglomerans), beta-carotene productions of 36 and 35 mg/L were obtained, respectively. No lycopene was detected in the beta-carotene production culture. pT-HB, constructed by addition of P. ananatis crtY gene into pT-LYCm4, was used for co-transformation with pSdxs and pSSN12Didi, which increased isopentenyl diphosphate and dimethylallyl diphosphate synthesis. beta-Carotene production significantly increased 1.5-fold (51 mg/L) with the amplification of the dxs gene through pSdxs and 4-fold (135 mg/L) with the mevalonate bottom pathway of pSSN12Didi in the presence of 3.3 mM mevalonate. The pT-DHB, constructed by integrating the dxs gene into pT-HB, was used for cotransformation of Escherichia coli (E. coli) harboring pSSN12Didi, resulting in beta-carotene production of 141 mg/L. Recombinant E. coli harboring pT-DHB and pSSN12Didi was used to maximize beta-carotene production by adjusting the available amounts of glycerol, a carbon source, and mevalonate, the precursor of the mevalonate bottom pathway. When recombinant E. coli was given 16.5 mM mevalonate and 2.5% (w/v) glycerol, beta-carotene production of 503 mg/L in concentration and 49.3 mg/g DCW in content was obtained at 144 h, which was the highest level of carotenoid production in E. coli ever reported in the literature.

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PMID: 17500531 [PubMed - indexed for MEDLINE]


181: Br J Nutr. 2007 May;97(5):977-86.
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Plasma concentrations of carotenoids and vitamin C are better correlated with dietary intake in normal weight than overweight and obese elderly subjects.

Vioque J, Weinbrenner T, Asensio L, Castelló A, Young IS, Fletcher A.

Departamento Salud Pública, Campus San Juan, Universidad Miguel Hernández, Elche-Alicante, Ctra. Valencia s/n, 03550 Alicante, Spain. vioque@umh.es

Carotenoid and vitamin C intakes, assessed by FFQ, have been positively associated with plasma concentrations in different populations. However, the influence of BMI on these associations has not been explored in detail. We explored in a cross-sectional study the relation between dietary carotenoid and vitamin C intakes, using a 135-item FFQ, with their plasma concentrations by BMI categories in 252 men and 293 women, 65 years and older. For men and women combined, significant (P < 0.05) Pearson correlations were observed between energy-adjusted dietary intakes and plasma concentrations (carotenoids adjusted for cholesterol) for: alpha-carotene 0.21, beta-carotene 0.19, lycopene 0.18, beta-cryptoxanthin 0.20 and vitamin C 0.36. Multiple linear regression analyses showed that the intake of carotenoids and vitamin C were significant predictors of their respective plasma concentration (P<0.01), and that BMI was inversely associated with plasma concentration of carotenoids (P< or =0.01) but not with plasma vitamin C. In addition, we observed significant interactions between BMI and the intakes of alpha-carotene and lutein + zeaxanthin, and to a lower extent beta-carotene, suggesting that these intakes in subjects with high BMI were not good predictors of their plasma concentration. The present data suggest that plasma carotenoids and vitamin C may be good markers of dietary intake in elderly subjects, but not so for alpha-carotene, beta-carotene and lutein + zeaxanthin in obese subjects.

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PMID: 17408529 [PubMed - indexed for MEDLINE]


182: Cancer Epidemiol Biomarkers Prev. 2007 May;16(5):962-8.
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Serum lycopene, other carotenoids, and prostate cancer risk: a nested case-control study in the prostate, lung, colorectal, and ovarian cancer screening trial.

Peters U, Leitzmann MF, Chatterjee N, Wang Y, Albanes D, Gelmann EP, Friesen MD, Riboli E, Hayes RB.

Cancer Prevention Program, Fred Hutchinson Cancer Research Center, P.O. Box 19024, 1100 Fairview Avenue North M4-B402, Seattle, WA 98109-1024, USA. upeters@fhcrc.org

BACKGROUND: Reports from several studies have suggested that carotenoids, and in particular lycopene, could be prostate cancer-preventive agents. This has stimulated extensive laboratory and clinical research, as well as much commercial and public enthusiasm. However, the epidemiologic evidence remains inconclusive. MATERIALS AND METHODS: We investigated the association between prediagnostic serum carotenoids (lycopene, alpha-carotene, beta-carotene, beta-cryptoxanthin, lutein, and zeaxanthin) and risk of prostate cancer in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, a multicenter study designed to examine methods of early detection and risk factors for cancer. The study included 692 incident prostate cancer cases, diagnosed 1 to 8 years after study entry, including 270 aggressive cases, with regional or distant stage (n = 90) or Gleason score >or=7 (n = 235), and 844 randomly selected, matched controls. As study participants were selected from those who were assigned to annual standardized screening for prostate cancer, results are unlikely to be biased by differential screening, a circumstance that is difficult to attain under non-trial conditions. RESULTS: No association was observed between serum lycopene and total prostate cancer [odds ratios (OR), 1.14; 95% confidence intervals (95% CI), 0.82-1.58 for highest versus lowest quintile; P for trend, 0.28] or aggressive prostate cancer (OR, 0.99; 95% CI, 0.62-1.57 for highest versus lowest quintile; P for trend, 0.433). beta-Carotene was associated with an increased risk of aggressive prostate cancer (OR, 1.67; 95% CI, 1.03-2.72 for highest versus lowest quintile; P for trend, 0.13); in particular, regional or distant stage disease (OR, 3.16; 95% CI, 1.37-7.31 for highest versus lowest quintile; P for trend, 0.02); other carotenoids were not associated with risk. CONCLUSION: In this large prospective study, high serum beta-carotene concentrations were associated with increased risk for aggressive, clinically relevant prostate cancer. Lycopene and other carotenoids were unrelated to prostate cancer. Consistent with other recent publications, these results suggest that lycopene or tomato-based regimens will not be effective for prostate cancer prevention.

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PMID: 17507623 [PubMed - indexed for MEDLINE]


183: Microbiology. 2007 May;153(Pt 5):1642-52.
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Identification and functional analysis of a phytoene desaturase gene from the extremely radioresistant bacterium Deinococcus radiodurans.

Xu Z, Tian B, Sun Z, Lin J, Hua Y.

Institute of Nuclear-Agricultural Sciences, Zhejiang University, 310029 Hangzhou, China.

The phytoene-related desaturases are the key enzymes in the carotenoid biosynthetic pathway. The gene encoding phytoene desaturase in the deinoxanthin synthesis pathway of Deinococcus radiodurans was identified and characterized. Two putative phytoene desaturase homologues (DR0861 and DR0810) were identified by analysis of conserved amino acid regions, and the former displayed the highest identity (68 %) with phytoene desaturase of the cyanobacterium Gloeobacter violaceus. DR0861 gene knockout and dinucleotide-binding motif deletion resulted in the arrest of lycopene synthesis and the accumulation of phytoene. The colourless DR0861 knockout mutant became more sensitive to acute ionizing radiation and oxygen stress. Complementation of the mutant with a heterologous or homologous gene restored its pigment and resistance. The desaturase activity of DR0861 (crtI) was further confirmed by the assay of enzyme activity in vitro and heterologous expression in Escherichia coli containing crtE and crtB genes (responsible for phytoene synthesis) from Erwinia uredovora. In addition, the amount of lycopene synthesis in E. coli resulting from the expression of crtI from D. radiodurans was determined, and this had significant dose-dependent effects on the survival rate of E. coli exposed to hydrogen peroxide and ionizing radiation.

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PMID: 17464079 [PubMed - indexed for MEDLINE]


184: Mol Nutr Food Res. 2007 May;51(5):609-17.
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Antioxidant nutritional quality of tomato.

Frusciante L, Carli P, Ercolano MR, Pernice R, Di Matteo A, Fogliano V, Pellegrini N.

Department of Soil, Plant and Environmental Sciences, University of Naples Federico II, Naples, Italy.

Regular consumption of tomatoes has been associated with decreased risk of chronic degenerative diseases. Epidemiological findings confirm the observed health effects are due to the presence of different antioxidant molecules such as carotenoids, particularly lycopene, ascorbic acid, vitamin E and phenol compounds, particularly flavonoids. In this work, eight components contributing to the healthy quality of tomato (i. e. lycopene, beta-carotene, other carotenoids, flavonoids, phenolic acids, vitamins C and E, dry residue) were studied in the framework of breeding programs aiming to develop nutritional superior genotypes. Twelve tomato advanced breeding lines and six open pollinated cultivars were grown in strictly controlled conditions and analysed for their content of antioxidants. Among the 18 genotypes analysed, 10 showed a high level of total carotenoids, 6 high level of beta-carotene, 9 high lycopene levels, 15 high flavonoids and 2 relevant concentration of vitamin E. Based on such data and on a literature survey on tomato composition, an index, called index of antioxidant nutritional quality (I(QUAN)), was proposed as a tool to address the breeding programs in selecting tomato genotypes with antioxidant nutritional qualities.

PMID: 17427261 [PubMed - indexed for MEDLINE]


185: Singapore Med J. 2007 May;48(5):415-20.
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Effect of lycopene from cooked tomatoes on serum antioxidant enzymes, lipid peroxidation rate and lipid profile in coronary heart disease.

Bose KS, Agrawal BK.

Department of Biochemistry, People's College of Medical Sciences and Research Centre, Bhanpur, Bhopal, India. subhashbose1@yahoo.co.in

INTRODUCTION: This present study aims to evaluate the beneficial effect of tomatoes, a rich source of lycopene, which is a relatively new carotenoid known to play an important role in human health and disease. METHODS: We investigated the lipid peroxidation rate by estimating malondialdehyde (MDA), levels of serum enzymes involved in antioxidant activities such as superoxide dismutase, glutathione peroxidase, glutathione reductase, reduced glutathione and lipid profile, which includes total cholesterol, triglycerides, high density lipoprotein, low density lipoprotein and very low density lipoprotein in a coronary heart disease (CHD) group and an age-matched control group. RESULTS: We observed significantly lower levels of serum antioxidant enzymes and very high lipid peroxidation rate in the CHD group, when compared to the controls (p-value is less than 0.001). At the same time, we observed significantly higher levels of lipids in the CHD group, when compared to the controls (p-value is less than 0.001). 60 days of tomato supplementation in the CHD group showed a significant improvement in the levels of serum enzymes involved in antioxidant activities and decreased lipid peroxidation rate (p-value is less than 0.001), but there were no significant changes in lipid profile (p-value is greater than 0.10). CONCLUSION: These findings suggest that tomato lycopene may have considerable therapeutic potential as an antioxidant but may not be used as a hypolipidaemic agent in CHD.

PMID: 17453080 [PubMed - indexed for MEDLINE]


186: Life Sci. 2007 Apr 10;80(18):1699-705. Epub 2007 Feb 3.
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Incorporation of lycopene into chylomicron remnant-like particles inhibits their uptake by HepG2 cells.

Bejta F, Napolitano M, Botham KM, Bravo E.

Department of Veterinary Sciences, The Royal Veterinary College, London, UK.

The influence of the incorporation of the antioxidant tomato pigment, lycopene, into chylomicron remnant-like particles (CRLPs) on their uptake by the liver cells was investigated. CRLPs or CRLPs containing lycopene (lycCRLPs) radiolabelled with [(3)H]triacylglycerol were incubated with cells of the human liver hepatoma cell line, HepG2, and the radioactivity taken up by the cells was determined. LycCRLPs were taken up significantly more slowly than CRLPs over a concentration range of 5-60 microg cholesterol/ml and a time course of 2-6 h. Pre-incubation of the hepatocytes with an excess of low density lipoprotein (LDL) inhibited the uptake of CRLPs by about 50%, but had no effect on the uptake of lycCRLPs, and under these conditions the CRLPs and lycCRLPs were taken up at similar rates. In HepG2 cells pre-treated with suramin, which inhibits uptake via the LDL receptor-related protein (LRP), the uptake of CRLPs was also inhibited (-37%) to a greater extent than that of lycCRLPs (-24%), so that the values for the two types of particle were no longer significantly different. Heparinase increased the uptake of lycCRLPs (about 2 fold), but not CRLPs, bringing it to a level equivalent to that seen with the control particles. These findings demonstrate that the incorporation of lycopene into CRLPs decreases their uptake by HepG2 cells and suggest that this effect is due to differential interaction with the LDL receptor and the LRP-receptor-mediated pathways, and may also involve binding of the particles to HSPG.

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PMID: 17328921 [PubMed - indexed for MEDLINE]


187: PLoS ONE. 2007 Apr 4;2(4):e350.
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Metabolic engineering of potato carotenoid content through tuber-specific overexpression of a bacterial mini-pathway.

Diretto G, Al-Babili S, Tavazza R, Papacchioli V, Beyer P, Giuliano G.

Ente per le Nuove Tecnologie, l'Energia e l'Ambiente (ENEA), Casaccia Research Center, Roma, Italy.

BACKGROUND: Since the creation of "Golden Rice", biofortification of plant-derived foods is a promising strategy for the alleviation of nutritional deficiencies. Potato is the most important staple food for mankind after the cereals rice, wheat and maize, and is extremely poor in provitamin A carotenoids. METHODOLOGY: We transformed potato with a mini-pathway of bacterial origin, driving the synthesis of beta-carotene (Provitamin A) from geranylgeranyl diphosphate. Three genes, encoding phytoene synthase (CrtB), phytoene desaturase (CrtI) and lycopene beta-cyclase (CrtY) from Erwinia, under tuber-specific or constitutive promoter control, were used. 86 independent transgenic lines, containing six different promoter/gene combinations, were produced and analyzed. Extensive regulatory effects on the expression of endogenous genes for carotenoid biosynthesis are observed in transgenic lines. Constitutive expression of the CrtY and/or CrtI genes interferes with the establishment of transgenosis and with the accumulation of leaf carotenoids. Expression of all three genes, under tuber-specific promoter control, results in tubers with a deep yellow ("golden") phenotype without any adverse leaf phenotypes. In these tubers, carotenoids increase approx. 20-fold, to 114 mcg/g dry weight and beta-carotene 3600-fold, to 47 mcg/g dry weight. CONCLUSIONS: This is the highest carotenoid and beta-carotene content reported for biofortified potato as well as for any of the four major staple foods (the next best event being "Golden Rice 2", with 31 mcg/g dry weight beta-carotene). Assuming a beta-carotene to retinol conversion of 6ratio1, this is sufficient to provide 50% of the Recommended Daily Allowance of Vitamin A with 250 gms (fresh weight) of "golden" potatoes.

PMID: 17406674 [PubMed]
PMCID: PMC1831493


188: Biochim Biophys Acta. 2007 Apr;1770(4):659-65. Epub 2006 Nov 23.
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Lycopene as a natural protector against gamma-radiation induced DNA damage, lipid peroxidation and antioxidant status in primary culture of isolated rat hepatocytes in vitro.

Srinivasan M, Sudheer AR, Pillai KR, Kumar PR, Sudhakaran PR, Menon VP.

Department of Biochemistry and Biotechnology, Annamalai University, Annamalainagar-608 002, Tamil Nadu, India.

The present study was designed to evaluate the radioprotective effect of lycopene, a naturally occurring dietary carotenoid, on gamma-radiation induced toxicity in cultured rat hepatocytes. The cellular changes were estimated using lipid peroxidative indices like thiobarbituric acid reactive substances (TBARS), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), reduced glutathione (GSH), ceruloplasmin, vitamins A, E, C and uric acid. The DNA damage was analysed by single cell gel electrophoresis (comet assay). The increase in the severity of DNA damage was observed with the increase in gamma-radiation dose (1, 2 and 4 Gy) in cultured rat hepatocytes. TBARS were increased significantly whereas the levels of GSH, vitamins C, E and A, ceruloplasmin, uric acid and antioxidant enzymes were significantly decreased in gamma-irradiated groups. The maximum damage to hepatocytes was observed at 4 Gy irradiation. Pretreatment with lycopene (1.86, 9.31 and 18.62 microM) showed a significant decrease in the levels of TBARS and DNA damage. The antioxidant enzymes increased significantly along with the levels of GSH, vitamins A, E, C, uric acid and ceruloplasmin. The maximum protection of hepatocytes was observed at 9.31 muM of lycopene pretreatment. Thus, our results show that pretreatment with lycopene offers protection against gamma-radiation induced cellular damage and can be developed as an effective radioprotector during radiotherapy.

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PMID: 17189673 [PubMed - indexed for MEDLINE]


189: Clin Nutr. 2007 Apr;26(2):252-63. Epub 2007 Mar 6.
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Lycopene differentially induces quiescence and apoptosis in androgen-responsive and -independent prostate cancer cell lines.

Ivanov NI, Cowell SP, Brown P, Rennie PS, Guns ES, Cox ME.

Prostate Research Centre at Vancouver General Hospital, University of British Columbia, 2660 Oak Street, Vancouver, BC, Canada V6T 1Z4.

BACKGROUND & AIMS: Lycopene has been credited with a number of health benefits including a decrease in prostate cancer risk. Our study investigates the molecular mechanism underlying anti-cancer activity of lycopene-based products in androgen-responsive (LNCaP) and androgen-independent (PC3) cells. METHODS: The effect of lycopene-based agents on prostate cancer growth and survival were examined using proliferation assays, bromodeoxyuridine incorporation and flow cytometric analysis of cellular DNA content. Biochemical effects of lycopene treatment were investigated by immunoblotting for changes in the absolute levels and phosphorylation states of cell cycle regulatory and signalling proteins. RESULTS: LNCaP and PC3 cells treated with the lycopene-based agents undergo mitotic arrest, accumulating in G0/G1 phase. Immunoblot screening indicated that lycopene's antiproliferative effects are likely achieved through a block in G1/S transition mediated by decreased levels of cyclins D1 and E and cyclin dependent kinase 4 and suppressed Retinoblastoma phosphorylation. These responses correlated with decreased insulin-like growth factor-I receptor expression and activation, increased insulin-like growth factor binding protein 2 expression and decreased AKT activation. Exposure to lycopene at doses as low as 10 nM for 48 h induced a profound apoptotic response in LNCaP cells. In contrast PC3 cells were resistant to apoptosis at doses up to 1 microM. CONCLUSIONS: Lycopene exposure can suppress phosphatidylinositol 3-kinase-dependent proliferative and survival signalling in androgen-responsive LNCaP and androgen-independent PC3 cells suggesting that the molecular mechanisms for the cytostatic and cytotoxic actions of lycopene involve induction of G0/G1 cell cycle arrest. This study supports further examination of lycopene as a potential agent for both the prevention and treatment of prostate cancer.

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PMID: 17337101 [PubMed - indexed for MEDLINE]


190: Mol Microbiol. 2007 Apr;64(2):448-60.
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Identification and biochemical characterization of a novel carotenoid oxygenase: elucidation of the cleavage step in the Fusarium carotenoid pathway.

Prado-Cabrero A, Estrada AF, Al-Babili S, Avalos J.

Department of Genetics, Faculty of Biology, University of Seville, E-41012 Seville, Spain.

The synthesis of the acidic apo-carotenoid neurosporaxanthin by the fungus Fusarium fujikuroi depends on four enzyme activities: phytoene synthase and carotene cyclase, encoded by the bifunctional gene carRA, a carotene desaturase, encoded by carB, and a postulated cleaving enzyme converting torulene (C(40)) into neurosporaxanthin (C(35)). Based on sequence homology to carotenoid oxygenases, we identified the novel fungal enzyme CarT. Sequencing of the carT allele in a torulene-accumulating mutant of F. fujikuroi revealed a mutation affecting a highly conserved amino acid, and introduction of a heterologous carT gene in this mutant restored the ability to produce neurosporaxanthin, pointing to CarT as the enzyme responsible for torulene cleavage. Expression of carT in lycopene-accumulating E. coli cells resulted in the formation of minor amounts of apo-carotenoids, but no enzymatic activity was observed in beta-carotene-accumulating cells, indicating a preference for acyclic or monocyclic carotenes. The purified CarT enzyme efficiently cleaved torulene in vitro to produce beta-apo-4'-carotenal, the aldehyde corresponding to the acidic neurosporaxanthin, and was also active on other monocyclic synthetic substrates. In agreement with its role in carotenoid biosynthesis, the carT transcript levels are induced by light and upregulated in carotenoid-overproducing mutants, as already found for other car genes.

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PMID: 17493127 [PubMed - indexed for MEDLINE]


191: Regul Toxicol Pharmacol. 2007 Apr;47(3):327-8; author reply 329. Epub 2006 Nov 28.
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Comment on:


Risk assessment of lutein and lycopene.

Granado F, Olmedilla B.

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PMID: 17134809 [PubMed - indexed for MEDLINE]


192: Genet Mol Res. 2007 Mar 22;6(1):116-21.
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Cassava diversity in Brazil: the case of carotenoid-rich landraces.

Nassar N, Vizzotto CS, Schwartz CA, Pires OR Jr.

Departamento de Genética, Instituto de Ciências Biológicas, Universidade de Brasília, Brasília, DF, Brasil nagnassa@rudah.com.br

In Brazil, the center of cassava origin, cassava landraces have acquired through their domestication a large diversity in relation to many economic traits such as high content of carotenoids and excellent palatability among other characters. One of these clones, which has been grown by indigenous Brazilian farmers and is now being maintained in the University of Brasília gene bank, showed a high level of lycopene content (5 mg/kg viz. a viz. zero in common cultivars, and 12-20 mg/kg in tomato, a lycopene-rich vegetable). A second landrace called UnB 400 had a high content of beta-carotene, which reached 4 mg/kg.

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PMID: 17469060 [PubMed - indexed for MEDLINE]


193: BMC Plant Biol. 2007 Mar 2;7:11.
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Silencing of beta-carotene hydroxylase increases total carotenoid and beta-carotene levels in potato tubers.

Diretto G, Welsch R, Tavazza R, Mourgues F, Pizzichini D, Beyer P, Giuliano G.

ENEA, Casaccia Research Center, Rome, Italy. gianfranco.diretto@casaccia.enea.it

BACKGROUND: Beta-carotene is the main dietary precursor of vitamin A. Potato tubers contain low levels of carotenoids, composed mainly of the xanthophylls lutein (in the beta-epsilon branch) and violaxanthin (in the beta-beta branch). None of these carotenoids have provitamin A activity. We have previously shown that tuber-specific silencing of the first step in the epsilon-beta branch, LCY-e, redirects metabolic flux towards beta-beta carotenoids, increases total carotenoids up to 2.5-fold and beta-carotene up to 14-fold. RESULTS: In this work, we silenced the non-heme beta-carotene hydroxylases CHY1 and CHY2 in the tuber. Real Time RT-PCR measurements confirmed the tuber-specific silencing of both genes . CHY silenced tubers showed more dramatic changes in carotenoid content than LCY-e silenced tubers, with beta-carotene increasing up to 38-fold and total carotenoids up to 4.5-fold. These changes were accompanied by a decrease in the immediate product of beta-carotene hydroxylation, zeaxanthin, but not of the downstream xanthophylls, viola- and neoxanthin. Changes in endogenous gene expression were extensive and partially overlapping with those of LCY-e silenced tubers: CrtISO, LCY-b and ZEP were induced in both cases, indicating that they may respond to the balance between individual carotenoid species. CONCLUSION: Together with epsilon-cyclization of lycopene, beta-carotene hydroxylation is another regulatory step in potato tuber carotenogenesis. The data are consistent with a prevalent role of CHY2, which is highly expressed in tubers, in the control of this step. Combination of different engineering strategies holds good promise for the manipulation of tuber carotenoid content.

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PMID: 17335571 [PubMed - indexed for MEDLINE]
PMCID: PMC1828156


194: Am J Clin Nutr. 2007 Mar;85(3):762-9.
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Effect of dietary lutein and zeaxanthin on plasma carotenoids and their transport in lipoproteins in age-related macular degeneration.

Wang W, Connor SL, Johnson EJ, Klein ML, Hughes S, Connor WE.

Department of Medicine, Oregon Health and Science University, Portland, OR 97239-3098, USA. wangwe@ohsu.edu

BACKGROUND: Low dietary intakes and low plasma concentrations of lutein and zeaxanthin are associated with an increased risk of age-related macular degeneration (AMD). No studies have challenged AMD patients with a diet high in lutein and zeaxanthin. OBJECTIVE: The objective was to examine the effect of diets low or high in lutein and zeaxanthin on plasma carotenoids and their transport in AMD patients. DESIGN: Seven AMD patients and 5 control subjects were fed a low-lutein, low-zeaxanthin diet ( approximately 1.1 mg/d) for 2 wk, which was followed by a high-lutein, high-zeaxanthin diet ( approximately 11 mg/d) for 4 wk. Ten subjects continued the diet for 8 wk. Plasma and lipoprotein carotenoids were measured by HPLC. RESULTS: The high-lutein, high-zeaxanthin diet resulted in 2- to 3-fold increases in plasma concentrations of lutein and zeaxanthin and other carotenoids, except lycopene, in the AMD patients and the control subjects. With this diet, 52% of the lutein and 44% of the zeaxanthin were transported by HDL; approximately 22% of lutein and zeaxanthin was transported by LDL. Only 20-25% of alpha-carotene, beta-carotene, and lycopene was transported by HDL; 50-57% was transported by LDL. CONCLUSIONS: The AMD patients and control subjects responded similarly to a diet high in lutein and zeaxanthin; plasma carotenoid concentrations increased greatly in both groups, and the transport of carotenoids by lipoproteins was not significantly different between the groups. This finding suggests that abnormalities in the metabolism of lutein and zeaxanthin in AMD may reside in the uptake of lutein and zeaxanthin from the plasma and transport into the retina.

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PMID: 17344498 [PubMed - indexed for MEDLINE]


195: Br J Nutr. 2007 Mar;97(3):440-6.
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Differential effect of dietary antioxidant classes (carotenoids, polyphenols, vitamins C and E) on lutein absorption.

Reboul E, Thap S, Tourniaire F, André M, Juhel C, Morange S, Amiot MJ, Lairon D, Borel P.

INSERM, U476, Marseille, France.

Lutein is assumed to protect the human retina from blue light and oxidative stress and diminish the incidence of age-related macular degeneration. This antioxidant is commonly ingested with other dietary antioxidants. The aim of the present study was to assess whether the main dietary antioxidants, i.e. carotenoids, polyphenols and vitamins C and E, affect lutein absorption. We measured the effect of adding a mixture of antioxidants (500 mg vitamin C, 67 mg (100 IU) vitamin E and 1 g polyphenols) to a lutein-containing meal (18 mg) on the postprandial lutein response in the chylomicron-rich fraction in eight healthy men. Lutein response was weakest (-23 %; P=0 x 07) after ingestion of the meal containing antioxidants (21 x 9 (sem 4 x 6) v. 28 x 4 (sem 7 x 2) nmol x h/l). To assess the effect of each class of antioxidants and potential interactions, we subsequently evaluated the effect of various combinations of antioxidants on lutein uptake by human intestinal Caco-2 TC-7 cells. A full factorial design showed that both a mixture of polyphenols (gallic acid, caffeic acid, (+)-catechin and naringenin) and a mixture of carotenoids (lycopene plus beta-carotene) significantly (P<0 x 05) impaired lutein uptake by (-10 to-30 %), while vitamins C and E had no significant effect. Subsequent experiments showed that the aglycone flavanone naringenin was the only polyphenol responsible for the effect of the polyphenol mixture, and that the carotenoid effect was not carotenoid species-dependent. Taken together, the present results suggest that lutein absorption is not markedly affected by physiological concentrations of vitamins C and E but can be impaired by carotenoids and naringenin

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PMID: 17313704 [PubMed - indexed for MEDLINE]


196: Clin Chem. 2007 Mar;53(3):447-55. Epub 2007 Jan 18.
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Relationships of circulating carotenoid concentrations with several markers of inflammation, oxidative stress, and endothelial dysfunction: the Coronary Artery Risk Development in Young Adults (CARDIA)/Young Adult Longitudinal Trends in Antioxidants (YALTA) study.

Hozawa A, Jacobs DR Jr, Steffes MW, Gross MD, Steffen LM, Lee DH.

Division of Epidemiology and Community Health, School of Public Health, Department of Laboratory Medicine and Pathology, University of Minnesota Medical School, University of Minnesota, Minneapolis, MN 55454, USA.

BACKGROUND: Serum carotenoid concentrations relate inversely to cardiovascular disease incidence. To clarify the effect of carotenoids on atherosclerotic risk factors, we examined the association of circulating carotenoids with inflammation, oxidative stress, endothelial dysfunction, and smoking. METHODS: Black and white men and women in the Coronary Artery Risk Development in Young Adults study, ages 18 to 30 years at recruitment (1985-1986) from 4 US cities, were investigated over 15 years. We included 2048 to 4580 participants in analyses of the sum of serum alpha-carotene, beta-carotene, zeaxanthin/lutein, and beta-cryptoxanthin concentrations and of lycopene at year 0 and at year 7. RESULTS: The year 0 sum of 4 carotenoids was inversely associated (all P <0.05) with year 0 leukocyte count (slope per sum carotenoid SD, -0.17); year 7 fibrinogen (slope, -0.10); year 7 and year 15 C-reactive protein (slope, -0.12 and -0.09); and year 15 F(2)-isoprostanes (slope, -13.0), soluble P-selectin (slope, -0.48), and soluble intercellular adhesion molecule-1 (sICAM1; slope, -5.1). Leukocyte counts and sICAM1 and F(2)-isoprostane concentrations had stronger associations in smokers than in nonsmokers, and sICAM1 concentrations were higher in the highest carotenoid quartile in smokers than in the lowest carotenoid quartile in nonsmokers. Superoxide dismutase was positively associated with the sum of 4 carotenoids (slope, 0.12; P <0.01). Lycopene was inversely associated only with sICAM1. The year 7 carotenoid associations with these markers were mostly similar to those at year 0. CONCLUSIONS: Circulating serum carotenoids were associated, some interactively with smoking, in apparently beneficial directions with markers of inflammation, oxidative stress, and endothelial dysfunction.

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PMID: 17234732 [PubMed - indexed for MEDLINE]
PMCID: PMC2440581


197: Eukaryot Cell. 2007 Mar;6(3):533-45. Epub 2006 Nov 3.
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Carotenoid biosynthesis in the primitive red alga Cyanidioschyzon merolae.

Cunningham FX Jr, Lee H, Gantt E.

Department of Cell Biology and Molecular Genetics, Microbiology Building, Room 2202, Campus Drive, University of Maryland, College Park, MD 20742, USa. BuddyX@umd.edu

Cyanidioschyzon merolae is considered to be one of the most primitive of eukaryotic photosynthetic organisms. To obtain insights into the origin and evolution of the pathway of carotenoid biosynthesis in eukaryotic plants, the carotenoid content of C. merolae was ascertained, genes encoding enzymes of carotenoid biosynthesis in this unicellular red alga were identified, and the activities of two candidate pathway enzymes of particular interest, lycopene cyclase and beta-carotene hydroxylase, were examined. C. merolae contains perhaps the simplest assortment of chlorophylls and carotenoids found in any eukaryotic photosynthetic organism: chlorophyll a, beta-carotene, and zeaxanthin. Carotenoids with epsilon-rings (e.g., lutein), found in many other red algae and in green algae and land plants, were not detected, and the lycopene cyclase of C. merolae quite specifically produced only beta-ringed carotenoids when provided with lycopene as the substrate in Escherichia coli. Lycopene beta-ring cyclases from several bacteria, cyanobacteria, and land plants also proved to be high-fidelity enzymes, whereas the structurally related epsilon-ring cyclases from several plant species were found to be less specific, yielding products with beta-rings as well as epsilon-rings. C. merolae lacks orthologs of genes that encode the two types of beta-carotene hydroxylase found in land plants, one a nonheme diiron oxygenase and the other a cytochrome P450. A C. merolae chloroplast gene specifies a polypeptide similar to members of a third class of beta-carotene hydroxylases, common in cyanobacteria, but this gene did not produce an active enzyme when expressed in E. coli. The identity of the C. merolae beta-carotene hydroxylase therefore remains uncertain.

Publication Types:


PMID: 17085635 [PubMed - indexed for MEDLINE]
PMCID: PMC1828917


198: Eur J Clin Nutr. 2007 Mar;61(3):295-303. Epub 2006 Aug 16.
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Tomatoes versus lycopene in oxidative stress and carcinogenesis: conclusions from clinical trials.

Basu A, Imrhan V.

Medical Pathology, UCDavis Health System, Sacramento, CA, USA.

OBJECTIVE: To review the effects of tomato product supplementation, containing lycopene, on biomarkers of oxidative stress and carcinogenesis in human clinical trials. RESULTS: Supplementation of tomato products, containing lycopene, has been shown to lower biomarkers of oxidative stress and carcinogenesis in healthy and type II diabetic patients, and prostate cancer patients, respectively. Processed tomato products like tomato juice, tomato paste, tomato puree, tomato ketchup and tomato oleoresin have been shown to provide bioavailable sources of lycopene, with consequent increases in plasma lycopene levels versus baseline. Dietary fats enhance this process and should be consumed together with food sources of lycopene. The mechanisms of action involve protection of plasma lipoproteins, lymphocyte DNA and serum proteins against oxidative damage, and anticarcinogenic effects, including reduction of prostate-specific antigen, upregulation of connexin expression and overall decrease in prostate tumor aggressiveness. There is limited in vivo data on the health benefits of lycopene alone. Most of the clinical trials with tomato products suggest a synergistic action of lycopene with other nutrients, in lowering biomarkers of oxidative stress and carcinogenesis. CONCLUSIONS: Consumption of processed tomato products, containing lycopene, is of significant health benefit and can be attributed to a combination of naturally occurring nutrients in tomatoes. Lycopene, the main tomato carotenoid, contributes to this effect, but its role per se remains to be investigated.

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PMID: 16929242 [PubMed - indexed for MEDLINE]


199: In Vivo. 2007 Mar-Apr;21(2):189-204.
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Review. Facts and fiction of phytotherapy for prostate cancer: a critical assessment of preclinical and clinical data.

Von Löw EC, Perabo FG, Siener R, Müller SC.

Department of Urology, University Hospital, Bonn, Germany.

The objective of this work was to substantially review all preclinical and clinical data on phytochemicals, such as genistein, lycopene, curcumin, epigallocatechin-gallate, and resveratrol, in terms of their effects as a potential treatment of prostate cancer. It is known, that prostate cancer patients increasingly use complementary and alternative medicines in the hope of preventing or curing cancer. The preclinical data for the phytochemicals presented in this review show a remarkable efficacy against prostate cancer cells in vitro, with molecular targets ranging from cell cycle regulation to induction of apoptosis. In addition, well-conducted animal experiments support the belief that these substances might have a clinical activity on human cancer. However, it is impossible to make definite statements or conclusions on the clinical efficacy in cancer patients because of the great variability and differences of the study designs, small patient numbers, short treatment duration and lack of a standardised drug formulation. Although some results from these clinical studies seem encouraging, reliable or long-term data on tumor recurrence, disease progression and survival are unknown. At present, there is no convincing clinical proof or evidence that the cited phythochemicals might be used in an attempt to cure cancer of the prostate.

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PMID: 17436567 [PubMed - indexed for MEDLINE]


200: Int J Cancer. 2007 Mar 1;120(5):970-7.
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Prospective study of vitamins C, E, and A and carotenoids and risk of oral premalignant lesions in men.

Maserejian NN, Giovannucci E, Rosner B, Joshipura K.

Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA. nmaserej@post.harvard.edu

Case-control studies indicate that vitamins C, E, A and carotenoids decrease risk of oral premalignant lesions (OPLs) and oral cancer, but clinical trials have failed to find protective effects of beta-carotene and suggest that vitamin E may increase risk. The authors prospectively evaluated the association between intake of vitamins C, E, A and carotenoids and incidence of OPL. Participants were 42,340 men in the Health Professionals Follow-up Study who provided information on supplement use and diet every 2-4 years by food frequency questionnaire. The authors confirmed 207 clinically or histopathologically diagnosed OPL events occurring between 1986 and 2002 by medical record review. Multivariate-adjusted relative risks (RR) of OPL were calculated with proportional hazards models. Total intake of vitamin C, vitamin A or carotenoids was not significantly associated with OPL risk. Dietary vitamin C was significantly associated with reduced risk (quintile 5 vs. 1, RR = 0.52, 95% CI 0.31-0.85, p(trend) = 0.04), but no association with supplemental vitamin C was observed. Inverse associations were apparent for beta-cryptoxanthin and alpha-carotene intake. No clear relationship emerged with beta-carotene, lycopene or lutein/zeaxanthin. Vitamin E was associated with increased risk (quintile 5 vs. 1, RR = 1.86, 95% CI 1.06-3.19), particularly among current smokers and with supplemental intake (current-smokers, supplement dose tertile 3 vs. 1, RR = 3.07, 95% CI 1.28-7.34, p(trend) = 0.01). For current smokers, beta-carotene also increased risk. Vitamin C from dietary sources, but not supplements, was associated with a reduced risk of OPL. The observed increased risk for current smokers with high vitamin E or beta-carotene intake should be explored further. Copyright 2006 Wiley-Liss, Inc.

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PMID: 17163413 [PubMed - indexed for MEDLINE]

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