Department of Medicine, Northwestern University, Lurie 6-105 303 E. Superior, Chicago, IL 60611, USA.
Cancer Metastasis Rev. 2010 Sep;29(3):465-82. doi: 10.1007/s10555-010-9238-z.
Genistein is a small, biologically active flavonoid that is found in high amounts in soy. This important compound possesses a wide variety of biological activities, but it is best known for its ability to inhibit cancer progression. In particular, genistein has emerged as an important inhibitor of cancer metastasis. Consumption of genistein in the diet has been linked to decreased rates of metastatic cancer in a number of population-based studies. Extensive investigations have been performed to determine the molecular mechanisms underlying genistein's antimetastatic activity, with results indicating that this small molecule has significant inhibitory activity at nearly every step of the metastatic cascade. Reports have demonstrated that, at high concentrations, genistein can inhibit several proteins involved with primary tumor growth and apoptosis, including the cyclin class of cell cycle regulators and the Akt family of proteins. At lower concentrations that are similar to those achieved through dietary consumption, genistein can inhibit the prometastatic processes of cancer cell detachment, migration, and invasion through a variety of mechanisms, including the transforming growth factor (TGF)-beta signaling pathway. Several in vitro findings have been corroborated in both in vivo animal studies and in early-phase human clinical trials, demonstrating that genistein can both inhibit human cancer metastasis and also modulate markers of metastatic potential in humans, respectively. Herein, we discuss the variety of mechanisms by which genistein regulates individual steps of the metastatic cascade and highlight the potential of this natural product as a promising therapeutic inhibitor of metastasis.
染料木黄酮是一种生物活性很强的小分子黄酮类化合物，在大豆中含量很高。这种重要的化合物具有多种生物学活性，但最著名的是它抑制癌症进展的能力。特别是，染料木黄酮已成为癌症转移的重要抑制剂。许多基于人群的研究表明，饮食中摄入染料木黄酮与转移性癌症发生率降低有关。已经进行了广泛的研究来确定染料木黄酮抗转移活性的分子机制，结果表明，这种小分子在转移级联的几乎每一步都具有显著的抑制活性。报告表明，在高浓度下，染料木黄酮可以抑制与原发性肿瘤生长和细胞凋亡有关的几种蛋白质，包括细胞周期调节蛋白的细胞周期蛋白类和 Akt 家族蛋白。在类似于通过饮食摄入所达到的较低浓度下，染料木黄酮可以通过多种机制抑制癌细胞脱落、迁移和侵袭的促转移过程，包括转化生长因子（TGF）-β信号通路。在体内动物研究和早期人体临床试验中均证实了几种体外发现，表明染料木黄酮既能抑制人类癌症转移，又能调节人类转移性潜力的标志物。在此，我们讨论了染料木黄酮调节转移级联各个步骤的多种机制，并强调了这种天然产物作为有前途的转移抑制剂的潜力。
