Toxins, 2016, 8(6).

Roles of Dietary Phytoestrogens on the Regulation of Epithelial-Mesenchymal Transition in Diverse Cancer Metastasis

Geum-A. Lee, Kyung-A. Hwang, Kyung-Chul Choi

Laboratory of Biochemistry and Immunology, College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk 361-763, Korea

Epithelial-mesenchymal transition (EMT) plays a key role in tumor progression. The cells undergoing EMT upregulate the expression of cell motility-related proteins and show enhanced migration and invasion. The hallmarks of EMT in cancer cells include changed cell morphology and increased metastatic capabilities in cell migration and invasion. Therefore, prevention of EMT is an important tool for the inhibition of tumor metastasis. A novel preventive therapy is needed, such as treatment of natural dietary substances that are nontoxic to normal human cells, but effective in inhibiting cancer cells. Phytoestrogens, such as genistein, resveratrol, kaempferol and 3,3′-diindolylmethane (DIM), can be raised as possible candidates. They are plant-derived dietary estrogens, which are found in tea, vegetables and fruits, and are known to have various biological efficacies, including chemopreventive activity against cancers. Specifically, these phytoestrogens may induce not only anti-proliferation, apoptosis and cell cycle arrest, but also anti-metastasis by inhibiting the EMT process in various cancer cells. There have been several signaling pathways found to be associated with the induction of the EMT process in cancer cells. Phytoestrogens were demonstrated to have chemopreventive effects on cancer metastasis by inhibiting EMT-associated pathways, such as Notch-1 and TGF-beta signaling. As a result, phytoestrogens can inhibit or reverse the EMT process by upregulating the expression of epithelial phenotypes, including E-cadherin, and downregulating the expression of mesenchymal phenotypes, including N-cadherin, Snail, Slug, and vimentin. In this review, we focused on the important roles of phytoestrogens in inhibiting EMT in many types of cancer and suggested phytoestrogens as prominent alternative compounds to chemotherapy.

瑞士《毒素》, 2016, 8(6).

膳食植物雌激素在不同肿瘤转移中对调节上皮-间充质细胞转型的作用

实验室的生化和免疫学、 兽医学、 忠北国立大学、 清州、 忠北 361 763、 韩国大学

上皮-间充质细胞转换 (EMT) 在肿瘤进展中起关键的作用。经历 EMT 上调细胞表达细胞运动相关蛋白并显示增强迁移和侵袭。EMT在癌细胞中的标志包括改变细胞形态、增加细胞迁移和侵袭转移能力。因此，预防EMT是抑制肿瘤转移的重要手段。需要新的预防性治疗，例如对正常人细胞无毒但对抑制癌细胞有效的天然饮食物质。植物雌激素，例如染料木黄酮，白藜芦醇，山奈酚和3,3'-二吲哚基甲烷（DIM），可以作为可能的候选物。它们是植物性膳食雌激素，其在茶，蔬菜和水果中发现，并且已知具有各种生物学功效，包括对癌症的化学预防活性。具体而言，这些植物雌激素可以通过抑制各种癌细胞中的EMT过程诱导抗增殖，凋亡和细胞周期停滞，抗转移的作用。已经发现几种信号通路与癌细胞中EMT过程的诱导相关。通过抑制EMT相关的途径，如Notch-1和TGF-β信号传导，植物雌激素被证明对癌症转移具有化学预防作用。因此，植物雌激素可以通过上调上皮表型（包括E-钙粘蛋白）的表达和下调间充质表型（包括N-钙粘蛋白，蜗牛，Slug和波形蛋白）的表达来抑制或逆转EMT过程。这次研究，我们集中在抑制EMT的植物雌激素在许多类型的癌症的重要作用并建议植物雌激素作为化疗的重要替代化合物。