Chemopreventive and adjuvant therapeutic potential of pomegranate (Punica granatum) for human breast cancer
Chemopreventive and adjuvant therapeutic potential of pomegranate (Punica granatum) for human breast cancer
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DOI：
10.1023/a:1014405730585
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发表时间：
2002-02-01
影响因子：
3.8
通讯作者：
Lansky, E
中科院分区：
文献类型：
--
作者：
Kim, ND;Mehta, R;Lansky, E
新鲜有机石榴(Punica Granatum L.)将该优良品种的种子油加工成三种成分：发酵汁、果皮水浸出物和冷榨或超临界CO2萃取的种子油。暴露在额外的溶剂中，这三种成分中的每一种都会产生富含多酚的级分(多酚)。他们的作用，以及粗全油和粗发酵和未发酵浓缩果汁，在体外评估了对人类乳腺癌可能的化学预防或辅助治疗潜力。从发酵汁、果皮和油脂中提取的多酚可以抑制60-80%的芳香酶活性，从而抑制内源雌激素的生物合成。根据种子油发酵汁多酚和果皮多酚的不同，发酵汁和果皮多酚以及整个种子油在100到1,000杯/毫升的浓度范围内，对17-β-羟基类固醇脱氢酶1型的抑制率为34%到79%。在酵母雌激素筛选中(是的)，冷冻干燥的新鲜石榴汁对17-β-雌二醇的雌激素活性有55%的抑制作用；而冷冻干燥的石榴汁本身只显示出最小的雌激素作用。发酵液和果皮多酚对乳腺癌细胞株的抑制作用依次为雌激素依赖性(MCF-7)、雌激素非依赖性(MB-MDA-231)和正常人乳腺上皮细胞(MCF-10A)。在MCF-7和MB-MDA-231细胞中，发酵石榴汁多酚的抗增殖作用一直是新鲜石榴汁多酚的两倍。石榴籽油在100µg/ml时对MCF-7细胞的增殖抑制率为90%，10µg/ml时对MCF-7细胞侵袭的抑制率为75%，对雌激素受体阴性的转移性人乳腺癌细胞的凋亡率在50µg/ml时为54%。这一发现表明，进一步评估石榴在人类乳腺癌中的化学预防和辅助治疗应用的临床试验可能是合理的。
Fresh organically grown pomegranates (Punica granatum L.) of the Wonderful cultivar were processed into three components: fermented juice, aqueous pericarp extract and cold-pressed or supercritical CO2-extracted seed oil. Exposure to additional solvents yielded polyphenol-rich fractions ('polyphenols') from each of the three components. Their actions, and of the crude whole oil and crude fermented and unfermented juice concentrate, were assessed in vitro for possible chemopreventive or adjuvant therapeutic potential in human breast cancer. The ability to effect a blockade of endogenous active estrogen biosynthesis was shown by polyphenols from fermented juice, pericarp, and oil, which inhibited aromatase activity by 60-80%. Fermented juice and pericarp polyphenols, and whole seed oil, inhibited 17-beta-hydroxysteroid dehydrogenase Type 1 from 34 to 79%, at concentrations ranging from 100 to 1,000 mug/ml according to seed oil > fermented juice polyphenols > pericarp polyphenols. In a yeast estrogen screen (YES) lyophilized fresh pomegranate juice effected a 55% inhibition of the estrogenic activity of 17-beta-estradiol; whereas the lyophilized juice by itself displayed only minimal estrogenic action. Inhibition of cell lines by fermented juice and pericarp polyphenols was according to estrogen-dependent (MCF-7) > estrogen- independent (MB-MDA-231) > normal human breast epithelial cells (MCF-10A). In both MCF-7 and MB-MDA-231 cells, fermented pomegranate juice polyphenols consistently showed about twice the anti-proliferative effect as fresh pomegranate juice polyphenols. Pomegranate seed oil effected 90% inhibition of proliferation of MCF-7 at 100 mug/ml medium, 75% inhibition of invasion of MCF-7 across a Matrigel membrane at 10 mug/ml, and 54% apoptosis in MDA-MB-435 estrogen receptor negative metastatic human breast cancer cells at 50 mug/ml. In a %% murine mammary gland organ culture, fermented juice polyphenols effected 47% inhibition of cancerous lesion formation induced by the carcinogen 7,12-dimethylbenz[a]anthracene (DMBA). The findings suggest that clinical trials to further assess chemopreventive and adjuvant therapeutic applications of pomegranate in human breast cancer may be warranted.