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16 TH INTERNATIONAL SYMPOSIUM ON CAROTENOIDS Preventive effects of marine carotenoids on inflammatory bowel disease Masashi Hosokawa1 , Yumiko Yasui2 , Nana Mikami1 , Kazuo Miyashita 1 , Takuji Tanaka3 1Faculty of Fisheries Sciences, Hokkaido University, 041-8611, Hokkaido, Japan, hoso@fish.hokudai.ac.jp 2School of Veterinary Medicine, Rakuno Gakuen University, 069- 8501, Hokkaido, Japan 3The Tokai Cytopathology Institute: Cancer Research and Prevention, 500-8285, Gifu, Japan Carotenoids are a family of natural pigments with at least 700 members. Fruits and vegetables are the major sources of carotenoids in diets. Marine organisms also contain many kinds of carotenoids such as astaxanthin (AX) and fucoxanthin (FX). Ulcerative colitis and Crohn's disease are major forms of inflammatory bowel diseases (IBD), which are chronic uncontrolled inflammation of intestinal mucosa. The incidence of ulcerative colitis has risen sharply in the developed country in recent decades. In this study, we focused on carotenoids as good candidates to be used for the prevention and/or therapy for IBD. The effects of AX and FX on the experimental colitis induced by dextran sulfate sodium (DSS) in mice were investigated. AX and FX at 200 ppm in the diet significantly suppressed a DSS-induced mucosal colitis determined by histopathology score. Both carotenoids alsoinhibited the expression of pro-inflammatory cytokines such as interleukin-6 (IL-6) and IL-1 mRNA in the intestinal tissue. In addition, COX-2 and iNOS mRNA expressions were also suppressed by AX and FX. As nuclear factor-kappaB (NF-kB) activity plays a critical role in the inflammation, we further examined the NF-kB expression in the inflamed intestinal tissue. Immunohistopathology score showed reduction of NF-kB expression in mice fed AX and FX. The suppression of NF-kB- DNA binding was also observed in murine macrophage-like cells, RAW 264.7 treated with AX. Further, AX significantly inhibited the occurrence of colonic mucosal ulcers, dysplastic crypts, and colonic adenocarcinoma on colitis-associated colon carcinogenesis induced by azoxymethane (AOM) / DSS in mice at 20 weeks. These results indicate that AX and FX are potential preventive compounds for IBD. POSTERS SESSION 4 4.1. Effect of lycopene on the progression of atherosclerosis development in New Zealand White Rabbits Janine Kalkowski1 , Mandy Fechner1 , Kati Fröhlich2 , Mario Lorenz1 , Volker Böhm3 , Verena Stangl1 1Medizinische Klinik für Kardiologie und Angiologie, Campus Mitte, Charité – Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany, janine.kalkowski@charite.de, mandy.fechner@charite.de, mario.lorenz@charite.de, verena.stangl@charite.de 2Food GmbH Jena Analytik Consulting, Orlaweg 2, 07743 Jena, Germany, k.froehlich@food-jena.de 3Institute of Nutrition, Friedrich Schiller University Jena, Dornburger Str. 25-29, 07743 Jena, Germany, volker.boehm@uni-jena.de In the frame of the EU-funded project "LYCOCARD" (www.lycocard.com) the role of tomato products, in particular lycopene, in reduction of progression of cardiovascular diseases was studied in an animal model. Lycopene is the main carotenoid found in high concentrations in tomatoes. Strong epidemiological evidence suggests that lycopene may provide important protection against cardiovascular diseases. We aimed to investigate cardiovascular protective effects of lycopene on the progression of high fat-induced atherosclerosis in New Zealand White Rabbits. For that purpose, animals were divided into four groups with 9 animals each, that were fed either a standard diet, a high-cholesterol diet containing 0.5% cholesterol, a high-cholesterol diet containing placebo beadlets, or a high-cholesterol diet plus 5 mg/kg body weight/day of lycopene (in the form of lycopene beadlets) for a time period of 4 weeks. We found significantly elevated lycopene plasma levels in the lycopene treated group. This was associated with a 50% reduction in total cholesterol and LDL cholesterol serum levels in the lycopene group, compared to the high-cholesterol and the placebo group. However, we could not observe a significant decrease in the extent of atherosclerotic lesions in aortae of the lycopene group. In addition, no differences in the intima-media thickness between the groups were found. Endothelial-dependent and endothelial-independent vasodilation in isolated rabbit aortic and carotid rings was not different between all treated groups. In summary, lycopene supplementation for 4 weeks increased lycopene plasma levels in the animals. Although we found strongly reduced total and LDL cholesterol serum levels in the lycopene treated group, no significant differences in atherosclerotic lesions and morphological changes in the aortae could be detected. We thank for financial support by the European Community Sixth Framework Programme (LYCOCARD, IP: 2006-016213). 4.2. Beta-Cryptoxanthin inhibits phosphoinositide 3-kinase (PI3K) signaling and lung cancer cell motility Benchun Miao, Anita Iskandar, Xiang-Dong Wang Nutrition and Cancer Biology Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA 02111, USA, benchun.miao@tufts.edu, anita.iskandar@tufts.edu, xiang-dong.wang@tufts.edu Recent epidemiologic studies show that increased dietary intake or higher blood levels of beta-Cryptoxanthin (BCX) relates to a reduced 70 ACTA BIOLOGICA CRACOVIENSIA Series Botanica
CAROTENOIDS IN THE PREVENTION OF CANCER AND CARDIOVASCULAR DISEASE risk of cigarette smoking-induced lung carcinogenesis. Here we show that BCX is effective at inhibiting migration and invasion of alpha7-nicotinic acetylcholine receptor (alpha7-nAChR) positive lung cancer cells by suppressing actin remodeling, ruffling/lamellipodia formation, but not in alpha7-nAChR negative cells. We establish that inhibition of alpha7-nAChR expression and its mediated PI3K signaling pathways potentially contribute to these activities of BCX. The PI3K downstream molecules such as Rac1 and ARF6 contribute to inhibition of lamellipodia formation and cell motility by BCX. BCX-induced cell migration inhibition is attenuated by overexpression of constitutively active PI3K or mutant of PTEN, activators of alpha7-nAChR/PI3K signaling, constitutively active Rac1 or ARF6. Overall, our studies show that BCX is efficient at suppressing PI3K signaling and lung cancer cell motility, which might be one of the potential mechanisms for the chemopreventive effect of BCX against lung cancers. 4.3. Quenching effect on singlet oxygen, suppression against generation of reactive oxygen species and melanin synthesis in skin, and inhibition of multidrug resistance in cancer cells by capsorubin and capsanthin Hiroyuki Yasui1 , Takashi Maoka2 , József Molnár3 , Irén Vincze4 , Péter Molnár5 , József Deli6 , Gabriella Spengler3 , Attila Zalatnai7 1Department of Analytical and Bioinorganic Chemistry, Kyoto, Pharmaceutical University, Misasagi, Yamashina-ku Kyoto 607-8414, Japan, yasui@mb.kyoto-phu.ac.jp 2Research Institute for Production Development, 15 Shimogamo-morimoto-cho, Sakyo-ku, Kyoto 606-0805, Japan, maoka@mbox.kyoto-inet.or.jp 3Institute of Medical Microbiology and Immunobiology, University of Szeged, Dóm tér 10, H-6720 Szeged, Hungary, molnarj@comser.szote.u-szeged.hu, gspengler@ihmt.unl.pt 4Department of Organic Chemistry, University of Szeged, Dóm tér 8, H-6720 Szeged, Hungary, Vincze@chem.u-szeged.hu 5Department of Pharmacognosy, University of Pécs, Medical School, Rókus u. 2, H-7624 Pécs, Hungary, Peter.Molnar.@aok.pte.hu 6Department of Biochemistry and Medical Chemistry, University of Pécs, Medical School, Szigeti út 12, H-7624 Pécs, Hungary, Jozsef.Deli@aok.pte.hu 7 st 1 Department of Pathology and Cancer Reseach, Semmelweis University, Budapest, Üllõi út 26, H-1085, zalatnai@korb1.sote.hu Capsorubin and capsanthin showed strong quenching activity for singlet oxygen. These activities were about 32 times (for capsorubin) and 25 times (for capsanthin) higher than that of β-carotene. These carotenoids also effectively suppressed the generation of reactive oxygen species (ROS) in mouse skin by irradiation of UVA. UVB-exposure increased significantly melanin concentration in the human skin equivalent model (HSEM) after 17 days culture. Topical application of carotenoid decreased significantly melanin production in comparison with the UVB-exposed group, suggesting that capsanthin and capsorubin had potent suppressive effects against UVB-induced melanogenesis in the HSEM. Capsorubin and capasanthin enhanced the Rhodamine 123 accumulation in human MDR1-gen transfected mouse lymphoma cells and reduced the expression of multidrug resistance efflux pump in xenografted PZX-40/46 human pancreatic adenocarcinoma cells. Apoptosis was induced by these carotenoids in cancer cells. The presence of vitamin C might influence the biological actions of these carotenoids differently. This study, on the part of the Hungarian authors was supported by the grants Szeged Foundation for Cancer Research and OTKA K 76176 and OTKA K 83898 (Hungarian Scientific Research Foundation). Vol. 53, suppl. 1, 2011 17–22 July 2011, Krakow, Poland 4.4. The effect of 9-cis β-carotene on plasma lipid profile and atherosclerosis in LDL receptor-deficient mice Noa Relevy1,3 , Ayelet Harari1 , Iris Barshack1,2 , Ami Ben Amotz4 , Dror Harats1,2 , Aviv Shaish1 1The Bert Strassburger Lipid Center, Sheba Medical Center, Tel-Hashomer, 52621 Israel 2Sackler School of Medicine, Tel-Aviv University, Israel 3The Mina and Everard Goodman Faculty of Life Science, Bar-Ilan University, Ramat Gan 4NBT, Eilat, Israel, aviv.shaish@sheba.health.gov.il Introduction: Atherosclerosis, a major risk factor of cardiovascular disease, is a complex disease caused by interactions between oxidized lipoproteins, invading inflammatory cells and vascular wall cells. The pro-vitamin A, β-carotene is a precursor for retinol, retinal and retinoic-acid. The alga Dunaliella bardawil is a rich source for β-carotene which under specific conditions accumulates β-carotene, reaching 10% of its dry weight, composed of approximately 50% all-trans and 50% 9-cis β-carotene isomers. Previous studies in our laboratory showed that β-carotene rich Dunaliella powder reduced plasma cholesterol levels and atherosclerosis development in mouse models. Importantly, by using Dunaliella powder composed of different ratios of 9-cis to all-trans isomers, we found that the protective effect is 9-cis β-carotene dependent. Aim: In the current work we aimed to study the effect of isolated 9-cis β-carotene compared to 9-cis β-carotene-rich Dunaliella powder on plasma cholesterol levels and atherogenesis in female and male LDL Receptor knockout (LDL R-/-) mice fed high-fat Western diet. Results: In female mice, 9-cis β-carotene inhibited atherosclerosis development significantly, along with a trend of decreased plasma cholesterol levels compared to the control group; however, 9-cis β-carotene-rich Dunaliella was more effective. In male mice, 9-cis β-carotene increased plasma cholesterol levels and had no effect on atherogenesis. In contrast, 9-cis β-carotene-rich Dunaliella powder inhibited atherogenesis and lowered plasma cholesterol. Conclusions: The results show that 9-cis β-carotene rich Dunaliella powder is more effective in inhibition of atherogenesis than isolated 9-cis β-carotene. The difference in the effect of 9-cis β-carotene rich Dunaliella powder and isolated 9-cis β-carotene on atherogenesis suggests that the alga Dunaliella contains additional active ingredients that may play a role in inhibition of atherosclerosis. 4.5. Photoprotective effects of aromatic carotenoids in human dermal fibroblasts (hdF) Sarah Wagener, Kaya Lutter, Silke De Spirt, Wilhelm Stahl Institute of Biochemistry and Molecular Biology I, Heinrich-Heine- University Düsseldorf, Universitätsstraße 1, 40225 Düsseldorf, Germany, sarah.wagener@uni-duesseldorf.de Dihydroxyisorenieratene (DHIR) and isorenieratene (IR) are naturally occurring aromatic carotenoids. DHIR is produced by the Brevibacterium linens which is used for the production of red smear cheeses. It is an unsual carotenoid comprising phenolic and polyenic structural elements. To evaluate those structure-related properties of DHIR, luteine and IR were studied for comparison. Due to this unique structure and based on previous studies, which have shown a high antioxidative capacity (Martin et al., 2009), it was suggested that DHIR provides protection against UVB-induced cell damage. 71
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ACTA BIOLOGICA CRACOVIENSIA Series
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Patronage Mayor of the City of Krak
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Organizing Committee Małgorzata Ba
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Plenary lectures
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16 TH INTERNATIONAL SYMPOSIUM ON CA
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Session 1 Nutritional Carotenoids a
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NUTRITIONAL CAROTENOIDS AND THEIR I
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Page 31 and 32: Session 2 Photosynthesis, Photochem
Page 33 and 34: PHOTOSYNTHESIS, PHOTOCHEMISTRY, AND
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Page 48 and 49: Professor Dr. Hans-Dieter Martin 19
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Page 73: Session 5 Interaction of Carotenoid
Page 83 and 84: BIOSYNTHESIS, GENETICS, AND METABOL
Page 95: Session 7 Carotenoids and Vision
Page 105 and 106: MODEL SYSTEMS, COMPUTATIONAL AND IN
Page 111 and 112: Index of Authors Abe K 44 Abramchik
Page 113 and 114: Szõke E 58 Szolcsány J 58 Szurkow
Page 115 and 116: ROMEO JT. 1973. A chemotaxonomic st
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