Phytoestrogens and breast cancer: a complex story
Phytoestrogens and breast cancer: a complex story
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DOI：
10.1007/s10787-008-8020-0
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发表时间：
2008-10-01
影响因子：
5.8
通讯作者：
Hoagland, M. S.
中科院分区：
文献类型：
--
作者：
Helferich, W. G.;Andrade, J. E.;Hoagland, M. S.
染料木黄酮是一种具有雌激素活性的化合物，作为生物活性化合物的复杂混合物的组分存在于各种大豆产品中，其基质分布在确定染料木黄酮的总体雌激素生物活性中起重要作用。我们回顾了大豆生物活性化合物如何调节染料木黄酮刺激的雌激素依赖性肿瘤生长的数据。我们的研究集中在饮食染料木黄酮对雌激素（E）依赖性乳腺肿瘤生长的影响，在体外和体内。染料木黄酮增强E依赖性人乳腺癌肿瘤生长的增殖。以类似的方式，膳食染料木黄酮刺激化学诱导（NMU）乳腺癌啮齿动物模型中的肿瘤生长。染料木黄酮，染料木黄酮的糖苷，模拟生长类似于染料木黄酮和撤出染料木黄酮或染料木黄酮的结果在肿瘤消退。大豆加工的程度调节膳食染料木黄酮在体内的作用，因为大豆蛋白分离物是一种高度纯化和广泛使用的蛋白质来源，经加工含有低、中和高含量的异黄酮，以剂量依赖性方式刺激E依赖性乳腺肿瘤的生长。与更纯净的饮食相反，用同等染料木黄酮水平的大豆粉进行的研究没有刺激体内E依赖性乳腺癌肿瘤的生长。然而，与雌激素和染料木黄酮被撤回的对照组相比，这些肿瘤的大小也没有消退。雌激素靶基因pS2、孕激素受体和细胞周期蛋白D I的表达与E依赖性肿瘤的生长相关，并且一直观察到其响应于饮食染料木黄酮治疗而被诱导。为了评估饮食染料木黄酮是否与目前的抗雌激素乳腺癌治疗，如他莫昔芬（TAM）相互作用，我们植入E依赖性肿瘤卵巢切除无胸腺小鼠和管理雌二醇，雌二醇加TAM，或雌二醇，TAM，饮食染料木黄酮。在这些研究中，膳食染料木黄酮能够否定TAM对E刺激的肿瘤生长的抑制作用。总之，染料木黄酮可作为雌激素激动剂，导致体内E依赖性人乳腺癌肿瘤的增殖，其活性可通过复杂大豆食品中其他生物活性成分的存在来调节。此外，膳食染料木黄酮可以否定TAM对E刺激的MCF-7细胞肿瘤植入卵巢切除的无胸腺小鼠的生长的抑制作用。
Genistein is an isoflavone with oestrogenic activity that is present in a variety of soy products as a constituent of complex mixtures of bioactive compounds, whose matrix profiles play an important role in determining the overall oestrogenic bioactivity of genistein. We review data on how the profile of soy bioactive compounds can modulate genistein-stimulated oestrogen-dependent tumour growth. Our research has focused on the effects of dietary genistein on the growth of oestrogen (E)-dependent mammary tumours both in vitro and in vivo. Genistein enhances the proliferation of E-dependent human breast cancer tumour growth. In a similar manner, dietary genistein stimulates tumour growth in the chemically-induced (NMU) mammary cancer rodent model. Genistin, the glycoside of genistein, simulates growth similar to that of genistein and withdrawal of either genistein or genistin results in tumour regression. The extent of soy processing modulates the effects of dietary genistein in vivo as soy protein isolate, a highly purified and widely used source of protein that is processed to contain low, medium, and high amounts of isoflavones, stimulate the growth of the E-dependent mammary tumours in a dose dependent manner. In contrast to the more purified diets, studies with soy flour of equivalent genistein levels did not stimulate the growth of E-dependent breast cancer tumours in vivo. However, the size of these tumours also did not regress as compared with control groups in which oestrogen and genistein have been withdrawn. The expression of the oestrogen-target genes of pS2, progesterone receptor, and cyclin D I correlates with the growth of E-dependent tumours and has been consistently observed to be induced in response to treatment with dietary genistein. To evaluate whether dietary genistein interacts with current anti-oestrogen breast cancer therapies such as tamoxifen (TAM), we implanted E-dependent tumours into ovariectomized athymic mice and administered oestradiol, oestradiol plus TAM, or oestradiol, TAM, and dietary genistein. In these studies dietary genistein was able to negate the inhibitory effect of TAM on E-stimulated tumour growth. In summary, genistein can act as an oestrogen agonist resulting in proliferation of E-dependent human breast cancer tumours in vivo and its activity can be modulated by the presence of other bioactive components in complex soy foods. Additionally, dietary genistein can negate the inhibitory effects of TAM on E-stimulated growth of MCF-7 cell tumours implanted into ovariectomized athymic mice.