Mechanisms of action of the soy isoflavone genistein:: emerging role for its effects via transforming growth factor β signaling pathways
Mechanisms of action of the soy isoflavone genistein:: emerging role for its effects via transforming growth factor β signaling pathways
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DOI：
10.1093/ajcn/68.6.1418s
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发表时间：
1998-12-01
影响因子：
7.1
通讯作者：
Barnes, S
中科院分区：
文献类型：
--
作者：
Kim, H;Peterson, TG;Barnes, S
大豆异黄酮染料木黄酮可减弱正常细胞和癌细胞在生长因子及细胞因子刺激下的增殖。本文综述了我们目前对染料木黄酮潜在作用机制的理解。在哺乳动物细胞的膜制剂中，染料木黄酮是表皮生长因子（EGF）受体酪氨酸自磷酸化的一种强效且特异的抑制剂。然而，在一些它能抑制生长的细胞系统中，染料木黄酮并不改变EGF受体或其他被认为参与信号转导途径的酪氨酸激酶底物的酪氨酸磷酸化，这表明可能有其他机制对其作用负责。其他可能的机制包括抑制DNA拓扑异构酶II活性、调节细胞周期检查点以及抗血管生成和抗氧化活性。我们实验室的实验提出了一个新概念，即染料木黄酮可能通过调节转化生长因子（TGF）β1信号通路来抑制细胞生长。染料木黄酮作用与TGFβ1功能之间的这种联系得到了对遗传性出血性毛细血管扩张症（一种涉及调节TGFβ受体复合物形成和信号传导的蛋白质突变的遗传性疾病）患者研究的初步结果的支持，其中几名患者在饮用大豆饮品1周后症状显著减轻。这些临床前研究结合我们的细胞培养数据表明，染料木黄酮的作用机制即使不依赖于TGFβ1信号传导，也与之相关。
The soy isoflavone genistein attenuates growth factor- and cytokine-stimulated proliferation of both normal and cancer cells. This article reviews our current understanding of the potential mechanisms of action of genistein. In membrane preparations from mammalian cells, genistein is a potent and specific inhibitor of tyrosine autophosphorylation of the epidermal growth factor (EGF) receptor. However, in several cell systems in which it inhibits growth, genistein does not alter tyrosine phosphorylation of the EGF receptor or other tyrosine kinase substrates thought to be involved in signal transduction pathways, suggesting that other mechanisms may be responsible for its action. Alternatives include inhibition of DNA topoisomerase II activity, regulation of cell cycle checkpoints, and antiangiogenic and antioxidant activity. Experiments in our laboratory suggest a new concept, that genistein may inhibit cell growth by modulating transforming growth factor (TGF) beta 1 signaling pathways. Such a link between genistein action and TGF beta 1 function is supported by preliminary results of studies in patients with hereditary hemorrhagic telangiectasia (a genetic disorder involving mutations in proteins that regulate TGF beta receptor complex formation and signaling) in which several patients had dramatic attenuation of their symptoms after 1 wk of ingesting soy-based beverages. These preclinical studies in combination with our cell culture data suggest that the mechanism of genistein involves, if not requires, TGF beta 1-signaling.