Nutrients, 2014, 6(10):4218-72.

Impact of Soy Isoflavones on the Epigenome in Cancer Prevention

Maria Pudenz, Kevin Roth, Clarissa Gerhauser

Division Epigenomics and Cancer Risk Factors, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany

Isoflavones (IF) such as genistein are cancer preventive phytochemicals found in soy and other legumes. Epidemiological studies point to a reduced risk for hormone‑dependent cancers in populations following a typical Asian diet rich in soy products. IF act as phytoestrogens and prevent tumorigenesis in rodent models by a broad spectrum of bioactivities. During the past 10 years, IF were shown to target all major epigenetic mechanisms regulating gene expression, including DNA methylation, histone modifications controlling chromatin accessibility, and non-coding RNAs. These effects have been suggested to contribute to cancer preventive potential in in vitro and in vivo studies, affecting several key processes such as DNA repair, cell signaling cascades including Wnt-signaling, induction of apoptosis, cell cycle progression, cell proliferation, migration and invasion, epithelial-mesenchymal transition (EMT), metastasis formation and development of drug-resistance. We here summarize the state-of-the-art of IF affecting the epigenome in major hormone-dependent, urogenital, and gastrointestinal tumor types and in in vivo studies on anti-cancer treatment or developmental aspects, and short-term intervention studies in adults. These data, while often requiring replication, suggest that epigenetic gene regulation represents an important novel target of IF and should be taken into consideration when evaluating the cancer preventive potential of IF in humans.

瑞士《营养成分》，2014年10月

在癌症预防中，大豆异黄酮对表观基因组的影响

玛丽亚 普德斯、 凯文 罗斯、 克拉丽莎 格霍伊泽

德国癌症研究中心表观基因学和癌症危险因素部门

大豆异黄酮 （IF） 例如在大豆和其他豆科植物中发现的金雀异黄素是一种预防癌症的植物化学物质。流行病学研究指出富含大豆产品的传统亚洲饮食人群患激素依赖性癌症的风险降低。由于广泛的生物活性，IF在啮齿动物模型被用作植物雌激素和防止肿瘤发生的药物。在过去的 10 年间，IF被证实靶向所有调节基因表达的主要表观遗传机制，包括 DNA 甲基化，控制染色质可及性的组蛋白修饰子和非编码 RNAs。在体外和体内研究中这些影响被认为对癌症有预防的潜能，影响几个关键过程 例如DNA 修复，包括 Wnt 信号的细胞信号转导叶栅，诱导细胞凋亡、 细胞周期进展、 细胞增殖、 迁移及侵袭、 上皮-间充质细胞转换 (EMT)，转移瘤形成以及药物抗药性的发展。在这里我们总结了目前IF主要以激素依赖的形式影响表观基因组， 泌尿生殖道和胃肠道的肿瘤类型对抗癌治疗或发展方面的体内研究以及短期干预研究。这些数据，虽然经常需要复制，表明表观遗传基因调控代表了一个IF的重要新型靶点，并且当评估IF对人体的癌症预防潜能时应该被仔细考虑。