Journal of Nutritional Biochemistry, 2011, 22(8):723-31.

Synergistic chemoprotective mechanisms of dietary phytoestrogens in a select combination against prostate cancer

Rajeev Kumar, et al

Division of Endocrinology, Central Drug Research Institute (CSIR), Lucknow 226 001, India

Combination of dietary phytoestrogens with diverse molecular mechanisms may enhance their anticancer efficacy at physiological concentrations, as evidenced in epidemiological studies. A select combination of three dietary phytoestrogens containing 8.33 μM each of genistein (G), quercetin (Q) and biochanin A (B) was found to be more potent in inhibiting the growth of androgen-responsive prostate cancer cells (LNCaP) as well as DU-145 and PC-3 prostate cancer cells in vitro than either 25 μM of G, B or Q or 12.5+12.5 μM of G+Q, Q+B or G+B. Subsequent mechanistic studies in PC-3 cells indicated that the action of phytoestrogens was mediated both through estrogen receptor (ER)-dependent and ER-independent pathways as potent estrogen antagonist ICI-182780 (ICI, 5 μM) could not completely mask the synergistic anticancer effects, which were sustained appreciably in presence of ICI. G+Q+B combination was significantly more effective than individual compounds or their double combinations in increasing ER-β, bax (mRNA expression); phospho-JNK, bax (protein levels); and in decreasing bcl-2, cyclin E, c-myc (mRNA expression); phospho-AKT, phospho-ERK, bcl-2, proliferating cell nuclear antigen (protein levels) in PC-3 cells. Phytoestrogens also synergistically stimulated caspase-3 activity. Our findings suggest that selectively combining anticancer phytoestrogens could significantly increase the efficacy of individual components resulting in improved efficacy at physiologically achievable concentrations. The combination mechanism of multiple anticancer phytochemicals may be indicative of the potential of some vegetarian diet components to elicit chemopreventive effects against prostate cancer at their physiologically achievable concentrations, in vivo.

美国《营养生物化学杂志》，2011年8月

选择性合用膳食植物雌激素来对抗前列腺癌的协同化学防护机制

拉吉夫  库马尔等

印度药物研究总院 (CSIR)内分泌部

膳食植物雌激素与不同分子机制相结合可提高其在生理浓度时的抗癌作用，流行病学的研究证明了这一点。三种膳食植物雌激素包含8.33 uM的金雀异黄素 (G)、 槲皮素 (Q) 和鹰嘴豆雅素 A (B) 的选择性组合被发现在体外雄激素应激前列腺癌 (LNCaP) 以及DU-145 和 PC-3癌细胞中比 25 μM G、B、 Q 或 12.5 + 12.5 μM 的 G + Q，Q + B 或 G + B能够更强有力地抑制细胞生长。随后在 PC-3 细胞中的机理研究表明植物雌激素的作用通过雌激素受体 (ER)- 依赖性和 ER- 独立性通路调控当强效的雌激素拮抗剂 ICI 182780（ICI，5 μ M） 无法完全掩藏其协同抗癌的作用，当 ICI 存在时可以持续增长。G + Q + B 组合比单独化合物或其双组合在增加 PC-3 细胞中ER-β，bax （mRNA 表达）；以及磷酸-JNK，bax （蛋白水平）；并且在降低 bcl-2，细胞周期蛋白 E，c-myc （mRNA 表达）；磷酸化-AKT，磷酸化-ERK，bcl-2，增殖细胞核抗原 （蛋白质水平）方面更有效。植物雌激素还会协同刺激半胱氨酸蛋白酶-3的活性。我们的研究结果表明有选择性地结合抗癌植物雌激素能够显著提高单一组分的疗效，导致在生理上可实现浓度疗效的增强。多种抗癌植物化学物质的联合机理表明一些处于生理上可实现浓度的素食饮食成分对体内前列腺癌的化学预防作用的潜力。