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      • KCI등재후보

        Pomegranate Extracts Potently Suppress Proliferation, Xenograft Growth, and Invasion of Human Prostate Cancer Cells

        Ephraim P. Lansky,Wenguo Jiang,James Kumi-Diaka,Martin Albrecht,Lyndon M. Gommersall,Amit Patel,Robert E. Mansel,Ishak Neeman,Albert A. Geldof,Moray J. Campbell 한국식품영양과학회 2004 Journal of medicinal food Vol.7 No.3

        We completed a multicenter study of the effects of pomegranate cold-pressed (Oil) or supercritical CO2-extracted (S) seed oil, fermented juice polyphenols (W), and pericarp polyphenols (P) on human prostate cancer cell xenograft growth in vivo, and/or proliferation, cell cycle distribution, apoptosis, gene expression, and invasion across Matrigel, in vitro. Oil, W, and P each acutely inhibited in vitro proliferation of LNCaP, PC-3, and DU 145 human cancer cell lines. The dose of P required to inhibit cell proliferation of the prostate cancer cell line LNCaP by 50% (ED50) was 70 mg/mL, whereas normal prostate epithelial cells (hPrEC) were significantly less affected (ED50 5 250 mg/mL). These effects were mediated by changes in both cell cycle distribution and induction of apoptosis. For example, the androgen-independent cell line DU 145 showed a significant increase from 11% to 22% in G2/M cells (P , .05) by treatment with Oil (35 mg/mL) with a modest induction of apoptosis. In other cell lines/treatments, the apoptotic response predominated, for example, in PC-3 cells treated with P, at least partially through a caspase 3-mediated pathway. These cellular effects coincided with rapid changes in mRNA levels of gene targets. Thus, 4-hour treatment of DU 145 cells with Oil (35 mg/mL) resulted in significant 2.3 6 0.001-fold (mean 6 SEM) up-regulation of the cyclin-dependent kinase inhibitor p21(waf1/cip1) (P , .01) and 0.6 6 0.14-fold down-regulation of c-myc (P , .05). In parallel, all agents potently suppressed PC-3 invasion through Matrigel, and furthermore P and S demonstrated potent inhibition of PC-3 xenograft growth in athymic mice. Overall, this study demonstrates significant antitumor activity of pomegranate-derived materials against human prostate cancer.

      • KCI등재후보

        Differentiation-Promoting Activity of Pomegranate (Punica granatum) Fruit Extracts in HL-60 Human Promyelocytic Leukemia Cells

        Ephraim P. Lansky,Satoru Kawaii 한국식품영양과학회 2004 Journal of medicinal food Vol.7 No.1

        Differentiation refers to the ability of cancer cells to revert to their normal counterparts, and its induction rep-resents an important noncytotoxic therapy for leukemia, and also breast, prostate, and other solid malignancies. Flavonoidsare a group of differentiation-inducing chemicals with a potentially lower toxicology profile than retinoids. Flavonoid-richpolyphenol fractions from the pomegranate (Punica granatum) fruit exert anti-proliferative, anti-invasive, anti-eicosanoid, andpro-apoptotic actions in breast and prostate cancer cells and anti-angiogenic activities in vitroand in vivo. Here we testedflavonoid-rich fractions from fresh (J) and fermented (W) pomegranate juice and from an aqueous extraction of pomegranatepericarps (P) as potential differentiation-promoting agents of human HL-60 promyelocytic leukemia cells. Four assays wereused to assess differentiation: nitro blue tetrazolium reducing activity, nonspecific esterase activity, specific esterase activity,and phagocytic activity. In addition, the effect of these extracts on HL-60 proliferation was evaluated. Extracts W and P werestrong promoters of differentiation in all settings, with extract J showing only a relatively mild differentiation-promoting ef-fect. The extracts had proportional inhibitory effects on HL-60 cell proliferation. The results highlight an important, previ-ously unknown, mechanism of the cancer preventive and suppressive potential of pomegranate fermented juice and pericarpextracts.

      • KCI등재

        High Environmental Stress Yields Greater Tocotrienol Content While Changing Vitamin E Profiles of Wild Emmer Wheat Seeds

        Emily J. Watts,Yu Shen,Ephraim P. Lansky,Eviatar Nevo,Gerd Bobe,Maret G Traber 한국식품영양과학회 2015 Journal of medicinal food Vol.18 No.2

        Vitamin E is an essential human nutrient that was first isolated from wheat. Emmer wheat, the cereal of Old World agriculture and a precursor to durum wheat, grows wild in the Fertile Crescent. Evolution Canyon, Israel, provides a microsite that models effects of contrasting environments. The north-facing and south-facing slopes exhibit low and high stress environments, respectively. Wild emmer wheat seeds were collected from both slopes and seed tocochromanol contents measured to test the hypothesis that high stress alters emmer wheat seed tocol-omics. Seeds from high stress areas contained more total vitamin E (108 ± 15 nmol/g) than seeds from low stress environments (80 ± 17 nmol/g, P = .0004). Vitamin E profiles within samples from these different environments revealed significant differences in isoform concentrations. Within each region, β- plus γ-tocotrienols represented the highest concentration of wheat tocotrienols (high stress, P < .0001; low stress, P < .0001), while α-tocopherol represented the highest concentration of the tocopherols (high stress, P = .0002; low stress, P < .0001). Percentages of both δ-tocotrienol and δ-tocopherol increased in high stress conditions. Changes under higher stress apparently are due to increased pathway flux toward more tocotrienol production. The production of more δ-isoforms suggests increased flow through a divergent path controlled by the VTE1 gene. Hence, stress conditions alter plant responses such that vitamin E profiles are changed, likely an attempt to provide additional antioxidant activity to promote seed viability and longevity.

      • Chemopreventive Effects of Pomegranate Seed Oil on Skin Tumor Development in CD1 Mice

        Chandradhar Dwivedi,Justin J. Hora,Emily R. Maydew,Ephraim P. Lansky 한국식품영양과학회 2003 Journal of medicinal food Vol.6 No.3

        Pomegranate seed oil was investigated for possible skin cancer chemopreventive efficacy in mice. In the mainexperiment, two groups consisting each of 30, 4 5-week-old, female CD 1 mice were used. Both groups had skin cancer ini-tiated with an initial topical exposure of 7,12-dimethylbenzanthracene and with biweekly promotion using 12-O-tetrade-canoylphorbol 13-acetate (TPA). The experimental group was pretreated with 5% pomegranate seed oil prior to each TPA ap-plication. Tumor incidence, the number of mice containg at least one tumor, was 100% and 93%, and multiplicity, theaverage number of tumors per mouse, was 20.8 and 16.3 per mouse after 20 weeks of promotion in the control and pome-granate seed oil-treated groups, respectively (P, .05). In a second experiment, two groups each consisting of three CD 1 micewere used to assess the effect of pomegranate seed oil on TPA-stimulated ornithine decarboxylase (ODC) activity, an im-portant event in skin cancer promotion. Each group received a single topical application of TPA, with the experimental groupreceiving a topical treatment 1 h prior with 5% pomegranate seed oil. The mice were killed 5 h later, and ODC activity wasassessed by radiometric method. The experimental group showed a 17% reduction in ODC activity. Pomegrante seed oil (5%)significantly decreased (P, .05) tumor incidence, multiplicity, and TPA-induced ODC activity. Overall, the results highlightthe potential of pomegranate seed oil as a safe and effective chemopreventive agent against skin cancer.

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