Institut für Mangostan & natürliche Antioxidantien

LYCOPIN (Lycopene)

Aktuelle wissenschaftliche Studien | 31-50

31: Appl Microbiol Biotechnol. 2008 Apr;78(5):801-10. Epub 2008 Feb 1.
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Uncovering the gene knockout landscape for improved lycopene production in E. coli.

Alper H, Stephanopoulos G.

Department of Chemical Engineering, Massachusetts Institute of Technology, Room 56-469, Cambridge, MA 02139, USA.

Systematic and combinatorial genetic approaches for the identification of gene knockout and overexpression targets have been effectively employed in the improvement of cellular phenotypes. Previously, we demonstrated how two of these tools, metabolic modeling and transposon mutagenesis, can be combined to identify strains of interest spanning the metabolic landscape of recombinant lycopene production in Escherichia coli. However, it is unknown how to best select multiple-gene knockout targets. Hence, this study seeks to understand how the overall order of gene selection, or search trajectory, biases the exploration and topology of the metabolic landscape. In particular, transposon mutagenesis and selection were employed in the background of eight different knockout genotypes. Collectively, 800,000 mutants were analyzed in hopes of exhaustively identifying all advantageous gene knockout targets. Several interesting observations, including clusters of gene functions, recurrence, and divergent genotypes, demonstrate the complexity of mapping only one genotype to one phenotype. One particularly interesting mutant, the DeltahnrDeltayliE genotype, exhibited a drastically improved lycopene production capacity in basic minimal medium in comparison to the best strains identified in previous studies.

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PMID: 18239914 [PubMed - indexed for MEDLINE]

32: Biosci Rep. 2008 Apr;28(2):97-106.
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Relationships of body mass index with serum carotenoids, tocopherols and retinol at steady-state and in response to a carotenoid-rich vegetable diet intervention in Filipino schoolchildren(1).

Ribaya-Mercado JD, Maramag CC, Tengco LW, Blumberg JB, Solon FS.

Jean Mayer USDA Human Nutrition Research Center at Tufts University, Boston, Massachusetts, USA.

In marginally nourished children, information is scarce regarding the circulating concentrations of carotenoids and tocopherols, and physiological factors influencing their circulating levels. We determined the serum concentrations of carotenoids, tocopherols and retinol at steady state and in response to a 9-week vegetable diet intervention in 9-12-year-old girls (n=54) and boys (n=65) in rural Philippines. We determined cross-sectional relationships of BMI (body mass index) with serum micronutrient levels, and whether BMI is a determinant of serum carotenoid responses to the ingestion of carotenoid-rich vegetables. We measured dietary nutrient intakes and assessed inflammation by measurement of serum C-reactive protein levels. The children had low serum concentrations of carotenoids, tocopherols and retinol as compared with published values for similar-aged children in the U.S.A. The low serum retinol levels can be ascribed to inadequate diets and were not the result of confounding due to inflammation. Significant inverse correlations of BMI and serum all-trans-beta-carotene, 13-cis-beta-carotene, alpha-carotene, lutein, zeaxanthin and alpha-tocopherol (but not beta-cryptoxanthin, lycopene and retinol) were observed among girls at baseline. The dietary intervention markedly enhanced the serum concentrations of all carotenoids. Changes in serum all-trans-beta-carotene and alpha-carotene (but not changes in lutein, zeaxanthin and beta-cryptoxanthin) in response to the dietary intervention were inversely associated with BMI in girls and boys. Thus, in Filipino school-aged children, BMI is inversely related to the steady-state serum concentrations of certain carotenoids and vitamin E, but not vitamin A, and is a determinant of serum beta- and alpha-carotene responses, but not xanthophyll responses, to the ingestion of carotenoid-rich vegetable meals.

PMID: 18384277 [PubMed - in process]

33: Carcinogenesis. 2008 Apr;29(4):816-23. Epub 2008 Feb 17.
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Lycopene inhibits IGF-I signal transduction and growth in normal prostate epithelial cells by decreasing DHT-modulated IGF-I production in co-cultured reactive stromal cells.

Liu X, Allen JD, Arnold JT, Blackman MR.

Endocrine Section, Laboratory of Clinical Investigation, Division of Intramural Research, National Center for Complementary and Alternative Medicine, National Institutes of Health, Bethesda, MD 20892, USA.

Prostate stromal and epithelial cell communication is important in prostate functioning and cancer development. Primary human stromal cells from normal prostate stromal cells (PRSC) maintain a smooth muscle phenotype, whereas those from prostate cancer (6S) display reactive and fibroblastic characteristics. Dihydrotestosterone (DHT) stimulates insulin-like growth factor-I (IGF-I) production by 6S but not PSRC cells. Effects of reactive versus normal stroma on normal human prostate epithelial (NPE or PREC) cells are poorly understood. We co-cultured NPE plus 6S or PRSC cells to compare influences of different stromal cells on normal epithelium. Because NPE and PREC cells lose androgen receptor (AR) expression in culture, DHT effects must be modulated by associated stromal cells. When treated with camptothecin (CM), NPE cells, alone and in stromal co-cultures, displayed a dose-dependent increase in DNA fragmentation. NPE/6S co-cultures exhibited reduced CM-induced cell death with exposure to DHT, whereas NPE/PRSC co-cultures exhibited CM-induced cell death regardless of DHT treatment. DHT blocked CM-induced, IGF-I-mediated, NPE death in co-cultured NPE/6S cells without, but not with, added anti-IGF-I and anti-IGF-R antibodies. Lycopene consumption is inversely related to human prostate cancer risk and inhibits IGF-I and androgen signaling in rat prostate cancer. In this study, lycopene, in dietary concentrations, reversed DHT effects of 6S cells on NPE cell death, decreased 6S cell IGF-I production by reducing AR and beta-catenin nuclear localization and inhibited IGF-I-stimulated NPE and PREC growth, perhaps by attenuating IGF-I's effects on serine phosphorylation of Akt and GSK3beta and tyrosine phosphorylation of GSK3. This study expands the understanding of the preventive mechanisms of lycopene in prostate cancer.

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PMID: 18283040 [PubMed - indexed for MEDLINE]

34: Photochem Photobiol Sci. 2008 Apr;7(4):492-7. Epub 2008 Mar 13.
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Identification of 3,4-didehydrorhodopin as major carotenoid in Rhodopseudomonas species.

Mizoguchi T, Isaji M, Harada J, Tamiaki H.

Department of Bioscience and Biotechnology, Faculty of Science and Engineering, Ritsumeikan University, Kusatsu, Shiga 525-8577, Japan.

Recently we isolated the purple photosynthetic bacterium, Rhodopseudomonas sp. Rits, which was phylogenetically related to Rhodopseudomonas (Rps.) palustris. In this study, the light-dependent and time-dependent changes in the carotenoid composition were investigated by HPLC analysis of extracts from the cultures. All seven carotenoids in the biosynthetic pathway from lycopene to spirilloxanthin were detected. Especially, 3,4-didehydrorhodopin, having twelve conjugated double bonds as well as one terminal hydroxy group, was isolated in a remarkably large amount and fully characterized for the first time. The biosynthetic intermediate was commonly found in the Rps. palustris strains (CGA009, Morita and NBRC100419).

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PMID: 18385894 [PubMed - indexed for MEDLINE]

35: Plant J. 2008 Apr;54(2):177-89. Epub 2008 Jan 16.
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Mutations of genes in synthesis of the carotenoid precursors of ABA lead to pre-harvest sprouting and photo-oxidation in rice.

Fang J, Chai C, Qian Q, Li C, Tang J, Sun L, Huang Z, Guo X, Sun C, Liu M, Zhang Y, Lu Q, Wang Y, Lu C, Han B, Chen F, Cheng Z, Chu C.

State Key Laboratory of Plant Genomics and National Centre for Plant Gene Research, Beijing 100101, China.

Pre-harvest sprouting (PHS) or vivipary in cereals is an important agronomic trait that results in significant economic loss. A considerable number of mutations that cause PHS have been identified in several species. However, relatively few viviparous mutants in rice (Oryza sativa L.) have been reported. To explore the mechanism of PHS in rice, we carried out an extensive genetic screening and identified 12 PHS mutants (phs). Based on their phenotypes, these phs mutants were classified into three groups. Here we characterize in detail one of these groups, which contains mutations in genes encoding major enzymes of the carotenoid biosynthesis pathway, including phytoene desaturase (OsPDS), zeta-carotene desaturase (OsZDS), carotenoid isomerase (OsCRTISO) and lycopene beta-cyclase (beta-OsLCY), which are essential for the biosynthesis of carotenoid precursors of ABA. As expected, the amount of ABA was reduced in all four phs mutants compared with that in the wild type. Chlorophyll fluorescence analysis revealed the occurrence of photoinhibition in the photosystem and decreased capacity for eliminating excess energy by thermal dissipation. The greatly increased activities of reactive oxygen species (ROS) scavenging enzymes, and reduced photosystem (PS) II core proteins CP43, CP47 and D1 in leaves of the Oscrtiso/phs3-1mutant and OsLCY RNAi transgenic rice indicated that photo-oxidative damage occurred in PS II, consistent with the accumulation of ROS in these plants. These results suggest that the impairment of carotenoid biosynthesis causes photo-oxidation and ABA-deficiency phenotypes, of which the latter is a major factor controlling the PHS trait in rice.

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PMID: 18208525 [PubMed - indexed for MEDLINE]
PMCID: PMC2327239

36: Obes Surg. 2008 Mar 28. [Epub ahead of print]
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Hypocarotenemia After Bariatric Surgery: A Preliminary Study.

Granado-Lorencio F, Herrero-Barbudo C, Olmedilla-Alonso B, Blanco-Navarro I, Pérez-Sacristán B.

Unidad de Vitaminas, Servicio de Bioquímica Clínica, Hospital Universitario Puerta de Hierro, 28035, Madrid, Spain,

BACKGROUND: Dietary carotenoids have attracted a great deal of attention due to their potential clinical relevance in conditions such as age-related maculopathy, osteoporosis, cardiovascular disease, and cancer. Surgical procedures have become the primary treatment of severe obesity, although nutrient deficiencies are common and long-term metabolic sequelae remain unknown. Thus, our aim was to assess the carotenoid status in serum of subjects after obesity surgery. METHODS: We evaluated the status of lutein, zeaxanthin, alpha- and beta-cryptoxanthin, lycopene, alpha- and beta-carotene, and fat-soluble vitamins by a quality-controlled high-performance liquid chromatography method in serum of 53 patients. Subjects were consecutively included as they were monitored for nutritional status after Roux-en-Y gastric bypass (RYGBP) or biliopancreatic diversion (BPD). Average follow-up time was 18 and 14 months for each protocol, respectively. RESULTS: After obesity surgery, a consistent and continuous decline in all carotenoids to almost undetectable levels occurs, especially in those who underwent BPD diversion who, on average, displayed serum levels about one half to one third of those found in RYGBP patients. CONCLUSION: The hypocarotenemia observed after bariatric surgery may compromise the availability of carotenoids to tissues and the vitamin A status, reducing the fat-soluble antioxidant capacity and constituting an additional risk factor for several clinical conditions. Given the emerging role of carotenoids in disease prevention, dietary advice on carotenoid-rich and fortified foods or the use of supplements in these patients should be considered.

PMID: 18369683 [PubMed - as supplied by publisher]

37: Br J Nutr. 2008 Mar 12:1-7. [Epub ahead of print]
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The relationship between total plasma carotenoids and risk factors for chronic disease among middle-aged and older men.

Farwell WR, Michael Gaziano J, Norkus EP, Sesso HD.

Division of Aging, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.

Individual plasma carotenoids have been associated with various chronic diseases but little is known about the relationship between total plasma carotenoids and risk factors for chronic diseases. In the Physicians' Health Study, we examined 492 men free of CVD and cancer for the relationship between total plasma carotenoids (the sum of alpha-carotene, beta-carotene, lycopene, zeaxanthin, lutein and beta-cryptoxanthin) and a wide variety of factors that predict chronic disease. Multivariate linear and logistic regression was performed to calculate parameter estimates (95 % CI) and OR (95 % CI) for total plasma carotenoids. In linear regression models, BMI, hypertension, alcohol intake and plasma levels of each lipid parameter and alpha-tocopherol significantly predicted levels of total plasma carotenoids. Upon adjustment for multiple chronic disease risk factors, the OR for levels of total plasma carotenoids greater than or equal to the median ( >/= 1.301 mumol/l) was statistically significant for current smoking (OR 0.21; 95 % CI 0.06, 0.77), weekly alcohol ingestion (OR 2.30; 95 % CI 1.06, 4.99), daily alcohol ingestion (OR 2.46; 95 % CI 1.29, 4.67), each 100 mg/l increase in total cholesterol (OR 0.73; 95 % CI 0.58, 0.91), LDL-cholesterol (OR 1.48; 95 % CI 1.17, 1.89) and HDL-cholesterol (OR 1.58; 95 % CI 1.26, 1.99), each 100 mg/ml increase in intercellular adhesion molecule-1 (OR 0.70; 95 % CI 0.53, 0.93) and each 10 mumol/l increase in alpha-tocopherol (OR 1.33; 95 % CI 1.12, 1.57), using logistic regression. Few lifestyle and clinical risk factors appear to be related to levels of total plasma carotenoids; however, levels of biomarkers such as plasma lipids and alpha-tocopherol may be strongly related.

PMID: 18334043 [PubMed - as supplied by publisher]

38: Antioxid Redox Signal. 2008 Mar;10(3):475-510.
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Cancer chemoprevention through dietary antioxidants: progress and promise.

Khan N, Afaq F, Mukhtar H.

Department of Dermatology, University of Wisconsin, Madison, Wisconsin 53706, USA.

It is estimated that nearly one-third of all cancer deaths in the United States could be prevented through appropriate dietary modification. Various dietary antioxidants have shown considerable promise as effective agents for cancer prevention by reducing oxidative stress which has been implicated in the development of many diseases, including cancer. Therefore, for reducing the incidence of cancer, modifications in dietary habits, especially by increasing consumption of fruits and vegetables rich in antioxidants, are increasingly advocated. Accumulating research evidence suggests that many dietary factors may be used alone or in combination with traditional chemotherapeutic agents to prevent the occurrence of cancer, their metastatic spread, or even to treat cancer. The reduced cancer risk and lack of toxicity associated with high intake of fruits and vegetables suggest that specific concentrations of antioxidant agents from these dietary sources may produce cancer chemopreventive effects without causing significant levels of toxicity. This review presents an extensive analysis of the key findings from studies on the effects of dietary antioxidants such as tea polyphenols, curcumin, genistein, resveratrol, lycopene, pomegranate, and lupeol against cancers of the skin, prostate, breast, lung, and liver. This research is also leading to the identification of novel cancer drug targets.

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PMID: 18154485 [PubMed - indexed for MEDLINE]

39: Biosci Biotechnol Biochem. 2008 Mar;72(3):677-85. Epub 2008 Mar 7.
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Characterizing the lipid-lowering effects and antioxidant mechanisms of tomato paste.

Hsu YM, Lai CH, Chang CY, Fan CT, Chen CT, Wu CH.

Department of Biological Science and Technology, China Medical University, Taichung 404, Taiwan.

Lycopene is known to decrease cardiovascular risks. The objective of this study was to investigate the molecular mechanisms of tomato paste containing approximately 0.1% lycopene in regulating lipid metabolism and oxidation. Hamsters fed 3% or 9% tomato paste containing 0.2% cholesterol were subjected to total cholesterol (TC), low density lipoprotein (LDL), high density lipoprotein (HDL), and triglyceride (TG) measurements. Our results showed reduced rates of serum TC and LDL levels due to 9% tomato paste were 14.3% and 11.3% respectively. Concentrations of 3% and 9% of tomato paste after 8 weeks of feeding significantly increased serum HDL levels, by 19.4% and 28.8% respectively. After ingestion of tomato paste for 8 weeks, the plasma malondialdehyde (MDA) levels significantly decreased, by 80.18% and 89.33% respectively, as compared to the cholesterol group. MDA and diene conjugation assays indicated the potent antioxidant activity of the tomato paste. The increased activities of superoxide dismutases (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px), further supported the antioxidant effects of the tomato paste. Two dimension-gel electrophoresis (2-DE) analysis revealed that carbonic anhydrase III (CAIII) and adenylate kinase 2 (AK2) may be two important regulators involved in the anti-lipid and antioxidant effects of tomato paste, opening new insight into the nutritional value of tomato in public health promotion.

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PMID: 18323670 [PubMed - indexed for MEDLINE]

40: Br J Nutr. 2008 Mar;99(3):606-13.
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Effects of carrot and tomato juice consumption on faecal markers relevant to colon carcinogenesis in humans.

Schnäbele K, Briviba K, Bub A, Roser S, Pool-Zobel BL, Rechkemmer G.

Chair of the Biofunctionality of Food, Department of Food and Nutrition, Technical University of Munich, Hochfeldweg 1, 85350 Freising, Germany.

High intakes of carotenoid-rich fruits and vegetables are associated with a reduced risk of various cancers including colon cancer. A human intervention study with carrot and tomato juice should show whether a diet rich in carotenoids, especially high in beta-carotene and lycopene, can modify luminal processes relevant to colon carcinogenesis. In a randomised cross-over trial, twenty-two healthy young men on a low-carotenoid diet consumed 330 ml tomato or carrot juice per d for 2 weeks. Intervention periods were preceded by 2-week depletion phases. At the end of each study period, faeces of twelve volunteers were collected for chemical analyses and use in cell-culture systems. Consumption of carrot juice led to a marked increase of beta-carotene and alpha-carotene in faeces and faecal water, as did lycopene after consumption of tomato juice. In the succeeding depletion phases, carotenoid contents in faeces and faecal water returned to their initial values. Faecal water showed high dose-dependent cytotoxic and anti-proliferative effects on colon adenocarcinoma cells (HT29). These effects were not markedly changed by carrot and tomato juice consumption. Neither bile acid concentrations nor activities of the bacterial enzymes beta-glucosidase and beta-glucuronidase in faecal water changed after carrot and tomato juice consumption. Faecal water pH decreased only after carrot juice consumption. SCFA were probably not responsible for this effect, as SCFA concentrations and profiles did not change significantly. In summary, in the present study, 2-week interventions with carotenoid-rich juices led only to minor changes in investigated luminal biomarkers relevant to colon carcinogenesis.

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PMID: 18254985 [PubMed - indexed for MEDLINE]

41: Epidemiology. 2008 Mar;19(2):338-44.
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Reliability of plasma carotenoid biomarkers and its relation to study power.

Al-Delaimy WK, Natarajan L, Sun X, Rock CL, Pierce JJ; Women's Healthy Eating and Living (WHEL) Study Group.Collaborators (23)
Pierce JJ, Al-Delaimy WK, Rock CL, Faerber S, Newman VA, Flatt SW, Kealey S, Natarajan L, Parker BA, Karanja N, Rarick M, Caan BJ, Fehrenbacher L, Stefanick ML, Carlson RW, Thomson CA, Warnecke J, Gold EB, Scudder S, Wasserman L, Hollenbach KA, Jones LA, Theriault R.
Cancer Prevention and Control Program, Moores UCSD Cancer Center, University of California, San Diego, La Jolla, CA 92093-0901, USA.

BACKGROUND: The reliability of biomarkers profoundly impacts validity of their use in epidemiology and can have serious implications for study power and the ability to find true associations. We assessed reliability of plasma carotenoid levels over time and how it could influence study power through sample size and effect-size. METHODS: Plasma carotenoid levels were measured in a cohort study of 1323 women participating in the control arm of the Women's Healthy Eating and Living Study. We compared mean plasma levels at baseline, year 1, and year 4 of the study for alpha-carotene, beta-carotene, lycopene, lutein, and beta-cryptoxanthin. Reliability of these levels over time was assessed by Spearman correlations and intraclass correlation. RESULTS: We found limited variation in mean levels between any 2 time points. Variation did not exceed 8% for lycopene, lutein, and beta-cryptoxanthin, 15% for alpha-carotene, and 18% for beta-carotene. Spearman correlations for individual carotenoids over time varied between 0.50 and 0.80, with lycopene having the lowest correlation. Intraclass correlations ranged from 0.47 to 0.66 for carotenoids. CONCLUSION: Intraclass correlations for plasma carotenoids over a period of several years are acceptable for epidemiologic studies. However, such variation is enough to decrease statistical power and increase the sample size needed to detect a given effect.

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PMID: 18300693 [PubMed - indexed for MEDLINE]

42: J Nutr. 2008 Mar;138(3):538-43.
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Lycopene inhibits experimental metastasis of human hepatoma SK-Hep-1 cells in athymic nude mice.

Huang CS, Liao JW, Hu ML.

Department of Food Science and Biotechnology, National Chung-Hsing University, Taichung 40227, Taiwan.

Lycopene has been shown to inhibit tumor metastasis in vitro, but it is unclear whether lycopene is antimetastatic in vivo. Here, nude mice were orally supplemented 2 times per week for 12 wk with a low or high dose of lycopene [1 or 20 mg/kg body weight (BW)] or with beta-carotene (20 mg/kg BW). Two weeks after the beginning of supplementation, mice were injected once with human hepatoma SK-Hep-1 cells via the tail vein. Plasma levels of matrix metalloproteinase (MMP)-2 and vascular endothelial growth factor (VEGF) increased gradually in tumor-injected mice (tumor controls) following tumor injection but were markedly lowered by lycopene or beta-carotene supplementation. Ten weeks after tumor injection, mice were killed and tumor metastasis was found to be confined to the lungs. Compared with the tumor controls, high-lycopene supplementation lowered the mean number of tumors from 14 +/- 8 to 3 +/- 5 (P < 0.05) and decreased tumor cross-sectional areas by 62% (P < 0.05). High-lycopene supplementation also decreased the positive rate of proliferating cellular nuclear antigen (PCNA), the level of VEGF, and protein expressions of PCNA, MMP-9, and VEGF in lung tissues. However, high-lycopene increased the protein expression of nm23-H1 (an antimetastatic gene) by 133% (P < 0.001). For most variables measured, effects of lycopene were dose dependent and the effect of beta-carotene was between those of high-dose and low-dose lycopene. These results show that lycopene supplementation reduces experimental tumor metastasis in vivo and suggest that such an action is associated with attenuation of tumor invasion, proliferation, and angiogenesis.

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PMID: 18287363 [PubMed - indexed for MEDLINE]

43: J Nutr. 2008 Mar;138(3):482-6.
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In vitro micellarization and intestinal cell uptake of cis isomers of lycopene exceed those of all-trans lycopene.

Failla ML, Chitchumroonchokchai C, Ishida BK.

Department of Human Nutrition, The Ohio State University, Columbus, OH 43210, USA.

The ratio of cis and all-trans lycopene (LYC) in human and animal tissues exceeds that in foods. The basis for this difference remains unknown, although differences in their stability, transport, and metabolism have been suggested. Here, we systematically compared the digestive stability, efficiency of micellarization, and uptake and intracellular stability of cis and all-trans isomers of LYC and carotenes using the coupled in vitro digestion and Caco-2 human intestinal cell model. Aril and oil from the carotenoid-rich gac fruit (Momordica cochinchinensis Spreng) were cooked with rice to provide a natural source of LYC and carotenes. The ratio of cis:trans isomers of LYC and beta-carotene was similar before and after simulated gastric and small intestinal digestion with recovery of total carotenoids in the digesta exceeding 70%. Micellarization of cis isomers of LYC during digestion of meals with both gac aril and oil was significantly greater than that of the all-trans isomer but less than for the carotenes. Uptake of cis isomers of LYC by Caco-2 cells was similar to that of carotenes and significantly greater than all-trans LYC. Micellarized carotenoids were relatively stable in micelles incubated in the cell culture environment and after accumulation in Caco-2 cells. These data suggest that the greater bioaccessibility of cis compared with all-trans isomers of LYC contributes to the enrichment of the cis isomers in tissues and that gac fruit is an excellent source of bioaccessible LYC and provitamin A carotenoids.

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PMID: 18287353 [PubMed - indexed for MEDLINE]

44: J Toxicol Environ Health B Crit Rev. 2008 Mar;11(3-4):242-59.
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Role of hormonal and other factors in human prostate cancer.

Wigle DT, Turner MC, Gomes J, Parent ME.

McLaughlin Centre for Population Health Risk Assessment, Institute of Population Health, University of Ottawa, Ottawa, Ontario, Canada.

American men have a lifetime risk of about 18% for prostate cancer diagnosis. Large international variations in prostate cancer risks and increased risks among migrants from low- to high-risk countries indicate important roles for environmental factors. Major known risk factors include age, family history, and country/ethnicity. Type 2 diabetes appears to reduce risk, while high birth weight and adult height are linked to increased risk of aggressive prostate cancer. Limited evidence supports an association with a history of sexually transmitted infections. A previous meta-analysis of eight cohort studies indicated no associations with plasma androgen, estrogen, or sex hormone binding globulin (SHBG) levels. However, there were dose-response relationships with baseline plasma testosterone levels in two studies that adjusted for other serum hormones and obesity. Finasteride (a drug that blocks testosterone activation) reduced prostate cancer risk by 25%. Low-frequency genes linked to familial prostate cancer only explain a small fraction of all cases. Sporadic cases were linked to relatively common polymorphisms of genes involved in (1) androgen synthesis, activation, inactivation and excretion, (2) hormone and vitamin D receptors, (3) carcinogen metabolism, and (4) DNA repair. Epidemiologic evidence supports protective roles for dietary selenium, vitamin E, pulses, tomatoes/lycopene, and soy foods, and high plasma 1,25-dihydroxyvitamin D levels. There is inadequate evidence that vegetables, fruit, carotenoids, and vitamins A and C reduce risk and that animal fat, alpha-linoleic acid, meat, coffee, and tea increase risk. Two major cohort studies found dose-response relationships with dietary calcium intake. Total dietary energy intake may enhance risk. Limited evidence supports a protective role for physical activity and elevated risk for farmers and other men with occupational pesticide exposure, particularly to organochlorine compounds and phenoxy herbicides. There is inadequate evidence for a relationship with alcohol or smoking. Most known or suspected external risk factors may act through hormonal mechanisms, but our review found little supporting evidence, and substantial further research is needed.

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PMID: 18368555 [PubMed - indexed for MEDLINE]

45: Plant J. 2008 Mar;53(5):717-30. Epub 2007 Nov 6.
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Abscisic acid deficiency in the tomato mutant high-pigment 3 leading to increased plastid number and higher fruit lycopene content.

Galpaz N, Wang Q, Menda N, Zamir D, Hirschberg J.

Department of Genetics, Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem 91904, Israel.

Carotenoids are present in most tissues of higher plants where they play a variety of essential roles. To study the regulation of carotenoid biosynthesis, we have isolated novel mutations in tomato (Solanum lycopersicum) with altered pigmentation of fruit or flowers. Here we describe the isolation and analysis of a tomato mutant, high-pigment 3 (hp3), that accumulates 30% more carotenoids in the mature fruit. Higher concentrations of carotenoids and chlorophyll were also measured in leaves and the pericarp of green fruit. The mutation in hp3 had occurred in the gene for zeaxanthin epoxidase (Zep), which converts zeaxanthin to violaxanthin. Consequently, leaves of the mutant lack violaxanthin and neoxanthin, and flowers contain only minute quantities of these xanthophylls. The concentration in the hp3 mutant of abscisic acid (ABA), which is derived from xanthophylls, is 75% lower than the normal level, making hp3 an ABA-deficient mutant. The plastid compartment size in fruit cells is at least twofold larger in hp3 plants compared with the wild-type. The transcript level in the green fruit of FtsZ, which encodes a tubulin-like protein involved in plastid division, is 60% higher in hp3 than in the wild-type, suggesting that increased plastid division is responsible for this phenomenon. Elevated fruit pigmentation and plastid compartment size were also observed in the ABA-deficient mutants flacca and sitiens. Taken together, these results suggest that ABA deficiency in the tomato mutant hp3 leads to enlargement of the plastid compartment size, probably by increasing plastid division, thus enabling greater biosynthesis and a higher storage capacity of the pigments.

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PMID: 17988221 [PubMed - indexed for MEDLINE]

46: Protein Expr Purif. 2008 Mar;58(1):23-31. Epub 2007 Nov 19.
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Identification of an alternative translation initiation site for the Pantoea ananatis lycopene cyclase (crtY) gene in E. coli and its evolutionary conservation.

Kim SW, Jung WH, Ryu JM, Kim JB, Jang HW, Jo YB, Jung JK, Kim JH.

AceBiotech Co., Ltd., #114 Bio-Venture Center, KRIBB, Yuseong, Daejeon 305-806, Republic of Korea.

Previous sequence analyses of the lycopene cyclase gene (crt Y) from Pantoea ananatis revealed that translation of its protein product in Escherichia coli began at the ATG start codon. We found, however, that this enzyme could also be produced in E. coli without the ATG start codon present. Results of experiments using crt Y mutants revealed that a GTG (Val) sequence, located in-frame and 24 bp downstream of the ATG, could act as a potential start codon. Additionally, a point-mutated GTA (Val), replaced from alternative GTG start codon, also displayed its potential as a start codon although the strength as a translation initiation codon was considerably weak. This finding suggests that non-ATG codons, especially one base pairing with the anticodon (3'-UAC-5') in fMet-tRNA, might be also able to function as start codon in translation process. Furthermore, amino acid sequence alignment of lycopene cyclases from different sources suggested that a Val residue located within the N-terminus of these enzymes might be used as an alternative translation initiation site. In particular, presence of a conserved Asp, located in-frame and 12 bp upstream of potential start codon, supports this assumption in view of the fact that Asp (GAT or GAC) can function as part of the Shine-Dalgano sequence (AGGAGG).

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PMID: 18096401 [PubMed - indexed for MEDLINE]

47: Toxicol In Vitro. 2008 Mar;22(2):510-4. Epub 2007 Nov 7.
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Antigenotoxicity and antimutagenicity of lycopene in HepG2 cell line evaluated by the comet assay and micronucleus test.

Scolastici C, Alves de Lima RO, Barbisan LF, Ferreira AL, Ribeiro DA, Salvadori DM.

Department of Pathology, Botucatu Medical School, São Paulo State University, UNESP, SP, Brazil.

Epidemiological studies have provided evidence that high consumption of tomatoes effectively reduces the risk of reactive oxygen species (ROS)-mediated diseases such as cancer. Tomatoes are rich sources of lycopene, a potent singlet oxygen-quenching carotenoid. In addition to its antioxidant properties, lycopene shows an array of biological effects including antimutagenic and anticarcinogenic activities. In the present study, the chemopreventive action of lycopene was examined on DNA damage and clastogenic or aneugenic effects of H2O2 and n-nitrosodiethylamine (DEN) in the metabolically competent human hepatoma cell line (HepG2 cells). Lycopene at concentrations of 10, 25, and 50 microM, was tested under three protocols: before, simultaneously, and after treatment with the mutagen, using the comet and micronucleus assays. Lycopene significantly reduced the genotoxicity and mutagenicity of H2O2 in all of the conditions tested. For DEN, significant reductions of primary DNA damage (comet assay) were detected when the carotenoid (all of the doses) was added in the cell culture medium before or simultaneously with the mutagen. In the micronucleus test, the protective effect of lycopene was observed only when added prior to DEN treatment. In conclusion, our results suggest that lycopene is a suitable agent for preventing chemically-induced DNA and chromosome damage.

Publication Types:

PMID: 18077131 [PubMed - indexed for MEDLINE]

48: Wei Sheng Yan Jiu. 2008 Mar;37(2):228-30.
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[Several carotenoids of vegetable determinated by high performance liquid chromatography]

[Article in Chinese]

Zhao X, Pan L, Meng J, Wang Y, et al .

Institute for Nutrition and Food Safety, Chinese Center for Disease Control and Prevention, Beijing 100050, China.

OBJECTIVE: To detect alpha-carotene (alpha-C), beta-carotene (beta-C), cryptoxanthin (Cryp), lutein (Lut) and lycopene (Lyco) levels in vegetables. METHODS: A HPLC method with C30 column was used to detect several carotenoids at the wave length of 450 nm. A gradient elution method with methanol, methyl-t-butyl-ether and ammonium acetate solution was used to separate the carotenoids. RESULTS: The level of Lut, Cryp, alpha-c, beta-c and lycopene were linearly related with the peak area. The recoveries of the standard were between 94.7%-108.1%. The relative standard deviations were less than 4.62%. CONCLUSION: The method could be simple and credible. It could separate 5 carotenoids in vegetables simultaneously.

Publication Types:

PMID: 18589615 [PubMed - in process]

49: J Agric Food Chem. 2008 Feb 27;56(4):1408-14. Epub 2008 Feb 1.
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Factors affecting lycopene oxidation in oil-in-water emulsions.

Boon CS, Xu Z, Yue X, McClements DJ, Weiss J, Decker EA.

Department of Food Science, Chenoweth Laboratory, University of Massachusetts, Amherst 01003, USA.

Evidence that dietary lycopene decreases the risk for a number of health conditions has generated new opportunities for the addition of lycopene to functional foods. This work examined the potential of oil-in-water emulsions as a lycopene delivery system for foods. Oil-in-water emulsions containing lycopene were prepared using different kinds of surfactant (cationic, anionic, and nonionic) and oil types (corn oil, stripped corn oil, and hexadecane). The formation of fatty acid oxidation products and the degradation of lycopene and tocopherol were then monitored. Fatty acids and lycopene had greater stability in oil-in-water emulsions stabilized by cationic dodecyltrimethylammonium bromide (DTAB) or nonionic polyoxyethylene (23) lauryl ether than by anionic sodium dodecyl sulfate (SDS). Oxidative stability in the corn oil-in-water emulsions stabilized by SDS was in the following order: tocopherol<lycopene<fatty acids. When emulsions were prepared using different carrier oils, the lycopene stability was in the following order: nonstripped corn oil>hexadecane>tocopherol-stripped corn oil. Lycopene degradation rates were similar in emulsions with and without fatty acids, suggesting that lycopene loss was independent of the presence of fatty acids. These results suggest that the stability of lycopene in oil-in-water emulsions could be inhibited by altering the emulsion droplet interface and by the presence of tocopherols.

Publication Types:

PMID: 18237137 [PubMed - indexed for MEDLINE]

50: J Agric Food Chem. 2008 Feb 27;56(4):1241-50. Epub 2008 Feb 1.
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How does tomato quality (sugar, acid, and nutritional quality) vary with ripening stage, temperature, and irradiance?

Gautier H, Diakou-Verdin V, Bénard C, Reich M, Buret M, Bourgaud F, Poëssel JL, Caris-Veyrat C, Génard M.

INRA, UR1115 Plantes et Systèmes de culture Horticoles, Domaine St. Paul, Site Agroparc, Avignon, France.

The objective of this study was to understand the respective impact of ripening stage, temperature, and irradiance on seasonal variations of tomato fruit quality. During ripening, concentrations in reducing sugars, carotenes, ascorbate, rutin, and caffeic acid derivates increased, whereas those in titratable acidity, chlorophylls, and chlorogenic acid content decreased. Fruit temperature and irradiance affected final fruit composition. Sugars and acids (linked to fruit gustative quality) were not considerably modified, but secondary metabolites with antioxidant properties were very sensitive to fruit environment. Increased fruit irradiance enhanced ascorbate, lycopene, beta-carotene, rutin, and caffeic acid derivate concentrations and the disappearance of oxidized ascorbate and chlorophylls. Increasing the temperature from 21 to 26 degrees C reduced total carotene content without affecting lycopene content. A further temperature increase from 27 to 32 degrees C reduced ascorbate, lycopene, and its precursor's content, but enhanced rutin, caffeic acid derivates, and glucoside contents. The regulation by light and temperature of the biosynthesis pathways of secondary metabolites is discussed.

Publication Types:

PMID: 18237131 [PubMed - indexed for MEDLINE]

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