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RISS 인기검색어
- 검색키워드
- 저자 : J. Kumi-Diaka (검색결과 4 건)
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Influence of Genistein Isoflavone on Matrix Metalloproteinase-2 Expression in Prostate Cancer Cells
J.K. Kumi-Diaka,M. Hassanhi,K. Merchant,Vanessa Horman 한국식품영양과학회 2006 Journal of medicinal food Vol.9 No.4
We investigated the expression of matrix metalloproteinase (MMP)-2 in human LNCaP and PC3 prostate can-cer cell lines in response to genistein exposure. Initially we studied the phytosensitivity of the cells to genistein using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay to determine percentage cell viability/inhibition and the ter-minal deoxynucleotidyl transferase-mediated fluorescein-dUTP nick end-labeling apoptosis assay to assess the type of celldeath. The results revealed that genistein inhibited growth and proliferation in both PC3 (hormone-dependent) and LNCaP(hormone-independent) prostate cancer cell lines, that there was no significant difference in sensitivity to genistein betweenPC3 and LNCaP cells, and that the effect of genistein on the cells was dose- and time-dependent. The results also revealedthat inhibition of cell growth in both PC3 and LNCaP cells was predominantly due to apoptotic cell death. These results wereconsistent with data in previous studies. This was followed by determination of the MMP-2 profile in response to genisteintreatment. The results indicated a significant dose- and time-dependent inhibition of MMP-2 expression levels in both cells,with a highly significant negative correlation between MMP-2 levels and concentration of genistein. This is of phytothera-peutic significance in view of the pivotal role of MMP-2 expression in the pathogenesis of prostate cancer. Increasing ex-pression of MMPs has been identified in many human cancers, including prostate cancer. Our findings indicate that genisteincould be a potent therapeutic inhibitor of MMP-2 in line with current concepts of targeted treatment.
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Anticancer Activities of Pomegranate Extracts and Genistein in Human Breast Cancer Cells
M.A. Louis Jeune,J. Kumi-Diaka,J. Brown 한국식품영양과학회 2005 Journal of medicinal food Vol.8 No.4
Previous studies have demonstrated the anticarcinogenic activity of pomegranate extracts and genistein in aseries of human cancer cells. In the present study, the potential anticancer effects of pomegranate extracts and genistein oninhibition of cell proliferation and induction of apoptosis in human breast cancer cells was investigated. Human breast can-cer cells (MCF-7) were cultured as monolayers in complete RPMI 1640 medium. The cells were cultured for 48 hours to al-low growth and achieve about 80% confluence in 48-well culture plates, and then exposed to the agents for 24 hours in sin-gle and combination treatments. Post-treatment growth rate and apoptosis induction were assessed by the use of a series ofbioassayslactate dehydrogenase and 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetra-zolium (inner salt) for viability and cytotoxicity; acridine orange-ethidium bromide and terminal deoxyribonucleotidyl trans-ferase-mediated dUTP nick-end labeling assays for induction of apoptosis. Both pomegranate extracts and genistein had sig-nificant (dose- and time-dependent) cytotoxic and growth inhibition effects on MCF-7 cancer cells. Both growth inhibitionand cytotoxicity were significantly higher (P. .01) in the combination treatments than in the single treatments with eitheragent. The data revealed that both drugs in single and in combination treatments induced apoptosis in MCF-7 cells. Apop-totic induction in the combination treatments was significantly higher (P. .01) than in single treatments. Both pomegranateextracts and genistein inhibit the growth of MCF-7 breast cancer cells through induction of apoptosis, with combination treat-ment being more efficacious than single treatments.
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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.
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