Trends in Breast Cancer Prevention, 2016, pp23-50.

Genistein: Programming Against Breast Cancer

Coral A. Lamartiniere, Sarah B. Jenkins, Jun Wang

Department of Pharmacology and Toxicology, University of Alabama at Birmingham UAB Comprehensive Cancer Center, University of Alabama at Birmingham

Soy and its primary isoflavonic component, genistein, have been demonstrated to act via a novel mechanism for breast cancer chemoprevention, i.e. programming. Programming is defined as developmental modifications at the molecular level that result in permanent and irreversible modifications that determine how cells and tissues respond later in life, even in the absence of the initial effector. Depending on the chemical effector and the changes in the biochemical blue-print the adult host may be rendered more or less susceptible for biochemical insult. Exposure of prepubertal rats to physiological concentrations of genistein via the diet protects against chemically-induced mammary cancer. Genistein during the prepubertal period increases mammary protein expression of p-AKT, annexin A2, EGF-receptor, gelsolin and GTP-cyclohydrolase-1, while decreasing expression of cleaved-caspase-3 and protein disulfide-isomerase A3, actions consistent with increased cell proliferation and differentiation, cell turnover, and tissue remodeling. In mature rat mammary glands, cleaved-caspases-3 and 9, cleaved-poly(ADP-ribose) polymerase, fetuin B, β-casein and Ki-67 were increased, while tyrosine hydrolase, annexin A2, EGF-receptor, phosphoglycerate kinase-1, steroid receptor co-activators 1–3, and vascular endothelial growth factor-receptor-2 were down-regulated, actions consistent with increased apoptosis and reduced potential for carcinogenesis. Recent epidemiology reports confirm the laboratory findings on carcinogenesis, demonstrating that adolescent girls ingesting soy containing genistein are at reduced risk for breast cancer. Toxicology studies in animals and epidemiology with genistein and soy demonstrate little or no toxicity. We recommend clinical studies in adolescent girls to determine if soy and genistein can suppress mammary cancer development by programming for cell/tissue differentiation.

《乳腺癌预防的趋势》2016, pp23-50.

金雀异黄素︰ 对抗乳腺癌的过程

药理学和毒理学，阿拉巴马大学伯明翰 UAB 综合癌症中心，阿拉巴马大学伯明翰分校

大豆和其主要异黄酮成分，金雀异黄素，已证明是通过一种机制来预防乳房癌，即抗癌过程。抗癌过程被定义为在分子水平发展导致永久和不可逆转的修改，确定细胞和组织后来在生活中，即使在没有初始效应响应的情况下。根据化学效应物和生物化学蓝图中的变化，成年宿主可能或多或少对生化损伤敏感。通过饮食将青春期前大鼠暴露于生理浓度的染料木黄酮保护，使其免受化学诱导的乳腺癌发生。青春期期间的染料木黄酮增加p-AKT，膜联蛋白A2，EGF受体，凝溶胶蛋白和GTP-环化水解酶-1的乳腺蛋白表达，同时降低切割的胱天蛋白酶-3和蛋白质二硫键异构酶A3的表达，与增加的细胞一致的作用增殖和分化，细胞更新和组织重塑。在成熟大鼠乳腺中，切割的胱天蛋白酶-3和9，切割的聚（ADP-核糖）聚合酶，胎球蛋白B，β-酪蛋白和Ki-67增加，而酪氨酸水解酶，膜联蛋白A2，EGF-受体，磷酸甘油酸激酶-1，类固醇受体共激活因子1-3和血管内皮生长因子受体-2下调，调节符合增加癌细胞的凋亡和减少癌发生的可能性。最近的流行病学报告证实了癌症发生的实验室结果，表明摄入含有大豆的染料木黄酮的青少年女孩患乳腺癌的风险降低。在动物中的毒理学研究和用染料木黄酮和大豆进行的流行病学显示很少或没有毒性。我们建议在青少年女孩的临床研究，以确定大豆和染料木素是否可以通过抗癌过程为细胞/组织分化抑制乳腺癌的发展。