Molecular Nutrition & Food Research, 2013, 57(1):100–113.

Mechanisms underlying the dualistic mode of action of major soy isoflavones in relation to cell proliferation and cancer risks

Ivonne M. C. M. Rietjens, Ana M. Sotoca, Jacques Vervoort, et al

Division of Toxicology, Wageningen University, 6703 HE Wageningen, The Netherlands

Isoflavones are phytoestrogens that have been linked to both beneficial as well as adverse effects in relation to cell proliferation and cancer risks. The present article presents an overview of these seemingly contradicting health effects and of mechanisms that could be involved in this dualistic mode of action. One mechanism relates to the different ultimate cellular effects of activation of estrogen receptor (ER) α, promoting cell proliferation, and of ERβ, promoting apoptosis, with the major soy isoflavones genistein and daidzein activating especially ERβ. A second mode of action includes the role of epigenetics, including effects of isoflavones on DNA methylation, histone modification and miRNA expression patterns. The overview presented reveals that we are only at the start of unraveling the complex underlying mode of action for effects of isoflavones, both beneficial or adverse, on cell proliferation and cancer risks. It is evident that whatever model system will be applied, its relevance to human tissues with respect to ERα and ERβ levels, co-repressor and co-activator characteristics as well as its relevance to human exposure regimens, needs to be considered and defined.

德国《分子营养与食品研究》，2013年1月

重要的大豆异黄酮对细胞增殖和癌症风险机制的二元模式活性的机制

伊沃 M.C.M. 瑞特简尼斯，安娜 M. 苏淘卡，雅克 福沃特雌，等

荷兰瓦赫宁根大学毒理学学院

异黄酮是一种对细胞增殖和癌症风险既有益又不利的植物雌激素。本文综述了这些对健康看似矛盾的影响以及可能参与其中的二元模式机制。一种机制涉及雌激素受体 (ER) α不同的最终细胞活化，促进细胞增殖；而ERβ，促进细胞凋亡，其中主要的大豆异黄酮金雀异黄素和大豆黄酮激活尤其是 ERβ。第二种行动模式包括表观遗传学的作用，包括异黄酮对 DNA 甲基化、 组蛋白修饰和 miRNA 表达模式的作用。综述表明，我们只是开始揭开金雀异黄素作用的复杂基础模式，有利或不利，对细胞增殖和癌症风险。很明显，无论模型体系是否被应用，其与人体组织的 ERα 和 ERβ 水平、 共同抑制因子和共同激活剂的特点的相关性以及对人体暴露疗法的相关性，需要考虑和定义。