Kampa M, Hatzoglou A, Notas G, Damianaki A, Bakogeorgou E, Gemetzi C, Kouroumalis E, Martin P M, Castanas E
Laboratory of Experimental Endocrinology, School of Medicine, University of Crete, and University Hospital, Heraklion GR-71110, Greece.
Nutr Cancer. 2000;37(2):223-33. doi: 10.1207/S15327914NC372_16.
The effect of different wine antioxidant polyphenols (catechin, epicatechin, quercetin, and resveratrol) on the growth of three prostate cancer cell lines (LNCaP, PC3, and DU145) was investigated. A dose- and time-dependent inhibition of cell growth by polyphenols was found at nanomolar concentrations. The proliferation of LNCaP and PC3 cells was preferentially inhibited by flavonoids (catechin, epicatechin, and quercetin), whereas resveratrol was the most potent inhibitor of DU145 cell growth. Possible mechanisms of action were investigated: 1) The competition of polyphenols for androgen binding in LNCaP cells revealed significant interaction only in the case of high concentrations of quercetin, at least at five orders of magnitude higher than the concentrations needed for cell growth inhibition. All other phenols showed low interactions. 2) Oxygen species production after mitogen stimulation and H2O2 sensitivity of these cell lines did not correlate with the observed antiproliferative effects, ruling out such a mode of action. 3) NO production revealed two different patterns: LNCaP and DU145 cells produced high concentrations of NO, whereas PC3 cells produced low concentrations. Phorbol ester stimulation of cells did not reveal any additional effect in LNCaP and DU145 cells, whereas it enhanced the secretion of NO in PC3 cells. Polyphenols decreased NO secretion. This effect correlates with their antiproliferative action and the inhibition of inducible NO synthase. It is therefore proposed that the antiproliferative effect of polyphenols is mediated through the modulation of NO production. In conclusion, our data show a direct inhibitory effect of low concentrations of antioxidant wine phenols on the proliferation of human prostate cancer cell lines mediated by the production of NO, further suggesting potential beneficial effects of wine and other phenol-containing foods or drinks for the control of prostate cancer cell growth.
研究了不同葡萄酒抗氧化多酚（儿茶素、表儿茶素、槲皮素和白藜芦醇）对三种前列腺癌细胞系（LNCaP、PC3和DU145）生长的影响。在纳摩尔浓度下发现多酚对细胞生长具有剂量和时间依赖性抑制作用。黄酮类化合物（儿茶素、表儿茶素和槲皮素）优先抑制LNCaP和PC3细胞的增殖，而白藜芦醇是DU145细胞生长的最有效抑制剂。研究了可能的作用机制：1）多酚在LNCaP细胞中与雄激素结合的竞争仅在高浓度槲皮素的情况下显示出显著相互作用，至少比抑制细胞生长所需浓度高五个数量级。所有其他酚类显示出低相互作用。2）这些细胞系在有丝分裂原刺激后的氧物种产生和对H2O2的敏感性与观察到的抗增殖作用不相关，排除了这种作用模式。3）一氧化氮（NO）产生显示出两种不同模式：LNCaP和DU145细胞产生高浓度NO，而PC3细胞产生低浓度NO。佛波酯刺激细胞在LNCaP和DU145细胞中未显示出任何额外作用，而在PC3细胞中增强了NO的分泌。多酚降低了NO分泌。这种作用与其抗增殖作用和对诱导型NO合酶的抑制相关。因此，有人提出多酚的抗增殖作用是通过调节NO产生介导的。总之，我们的数据表明低浓度抗氧化葡萄酒酚对人前列腺癌细胞系增殖具有直接抑制作用，该作用由NO产生介导，进一步表明葡萄酒和其他含酚食物或饮料对控制前列腺癌细胞生长可能具有有益作用。
