Pomegranate extracts potently suppress proliferation, xenograft growth, and invasion of human prostate cancer cells

被引:158
作者
Albrecht, M
Jiang, WG
Kumi-Diaka, J
Lansky, EP
Gommersall, LM
Patel, A
Mansel, RE
Neeman, I
Geldof, AA
Campbell, MJ
机构
[1] Rimonest Ltd, Horev Ctr, Haifa, Israel
[2] Univ Marburg, Inst Anat & Cell Biol, Marburg, Germany
[3] Cardiff Univ, Dept Surg, Cardiff CF4 4XN, S Glam, Wales
[4] Univ Birmingham, Sch Med, Div Med Sci, Birmingham, W Midlands, England
[5] Florida Atlantic Univ, Coll Liberal Arts, Div Sci, Davie, FL USA
[6] Technion Israel Inst Technol, Dept Food Engn & Biotechnol, IL-32000 Haifa, Israel
[7] Vrije Univ Amsterdam Med Ctr, Dept Urol, Amsterdam, Netherlands
[8] Vrije Univ Amsterdam Med Ctr, Dept Nucl Med, Amsterdam, Netherlands
关键词
apoptosis; chemoprevention; flavonoid; p2 1((waf/cip1)); phytoestrogen; prostate cancer; punicic acid;
D O I
10.1089/1096620041938704
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
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 mug/mL, whereas normal prostate epithelial cells (hPrEC) were significantly less affected (ED50 = 250 mug/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 G(2)/M cells (P < .05) by treatment with Oil (35 mug/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 mug/mL) resulted in significant 2.3 +/- 0.001-fold (mean +/- SEM) up-regulation of the cyclin-dependent kinase inhibitor p21((waf1/cip1)) (P < .01) and 0.6 +/- 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.
引用
收藏
页码:274 / 283
页数:10
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