Shenouda Nader S, Zhou Christine, Browning Jimmy D, Ansell Pete J, Sakla Mary S, Lubahn Dennis B, Macdonald Ruth S
Department of Biochemistry and the Missouri University Center for Phytonutrient and Phytochemical Studies, University of Missouri, Columbia 65211, USA.
Nutr Cancer. 2004;49(2):200-8. doi: 10.1207/s15327914nc4902_12.
Prostate cancer is an important public health problem in the United States. Seven phytoestrogens found in common herbal products were screened for estrogen receptor binding and growth inhibition of androgen-insensitive (PC-3) and androgen-sensitive (LNCaP) human prostate tumor cells. In a competitive 3H-estradiol ligand binding assay using mouse uterine cytosol, 2.5 M quercetin, baicalein, genistein, epigallocatechin gallate (EGCG), and curcumin displaced > 85% of estradiol binding, whereas apigenin and resveratrol displaced > 40%. From growth inhibition studies in LNCaP cells, apigenin and curcumin were the most potent inhibitors of cell growth, and EGCG and baicalein were the least potent. In PC-3 cells, curcumin was the most potent inhibitor of cell growth, and EGCG was the least potent. In both cell lines, significant arrest of the cell cycle in S phase was induced by resveratrol and EGCG and in G2M phase by quercetin, baicalein, apigenin, genistein, and curcumin. Induction of apoptosis was induced by all of the 7 compounds in the 2 cell lines as shown by TUNEL and DNA fragmentation assays. Androgen responsiveness of the cell lines did not correlate with cellular response to the phytoestrogens. In conclusion, these 7 phytoestrogens, through different mechanisms, are effective inhibitors of prostate tumor cell growth.
前列腺癌是美国一个重要的公共卫生问题。对常见草药产品中发现的七种植物雌激素进行了雌激素受体结合以及对雄激素不敏感(PC-3)和雄激素敏感(LNCaP)人前列腺肿瘤细胞生长抑制作用的筛选。在使用小鼠子宫胞质溶胶的竞争性3H-雌二醇配体结合试验中,2.5μM的槲皮素、黄芩素、染料木黄酮、表没食子儿茶素没食子酸酯(EGCG)和姜黄素取代了>85%的雌二醇结合,而芹菜素和白藜芦醇取代了>40%。从对LNCaP细胞的生长抑制研究来看,芹菜素和姜黄素是最有效的细胞生长抑制剂,而EGCG和黄芩素的效果最差。在PC-3细胞中,姜黄素是最有效的细胞生长抑制剂,而EGCG的效果最差。在这两种细胞系中,白藜芦醇和EGCG诱导细胞周期在S期显著停滞,槲皮素、黄芩素、芹菜素、染料木黄酮和姜黄素则诱导细胞周期在G2M期停滞。TUNEL和DNA片段化分析显示,所有7种化合物在这两种细胞系中均诱导了细胞凋亡。细胞系的雄激素反应性与对植物雌激素的细胞反应无关。总之,这7种植物雌激素通过不同机制,是前列腺肿瘤细胞生长的有效抑制剂。