Effects of SOD2 genotype, oxidative stress, ER??, and genistein on prostate cance

SOD2 基因型、氧化应激、ER?? 和金雀异黄酮对前列腺癌的影响

• 批准号: 8115621
• 负责人: MAARTEN C BOSLAND
• 金额: $ 7.85万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-03-04 至 2013-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8115621
• 关键词: Address; Adverse effects; Affect; Affinity; Animal Model; Antioxidants; Apoptosis; Asians; Behavior; Belief; Binding; Breast Cancer Cell; Cancer Patient; Cell Proliferation; Cells; Chemopreventive Agent; Conflict (Psychology); Consumption; Country; DNA Binding; Data; Development; Dose; Environment; Enzymes; Equilibrium; Estrogen Receptors; Ethanol; Exposure to; Free Radical Scavenging; Genes; Genetic Polymorphism; Genistein; Genotype; Growth; Growth Factor Receptors; Human; Hydrogen Peroxide; In Vitro; Intake; Investigation; Isoflavones; Knowledge; Literature; Malignant Neoplasms; Malignant neoplasm of prostate; Manganese Superoxide Dismutase; Mediation; Meta-Analysis; Monitor; Output; Oxidation-Reduction; Oxidative Stress; Oxidoreductase; Oxygen; Pathway interactions; Patients; Physiological; Population; Property; Prostate; Reactive Oxygen Species; Research; Risk; SOD2 gene; Stress; Superoxide Dismutase; Testing; Therapeutic; Topoisomerase II; Tyrosine Kinase Inhibitor; Up-Regulation; Variant; Vitamin K 3; alanylalanine; angiogenesis; cancer cell; cancer risk; carcinogenesis; catalase; cell growth; glutathione peroxidase; high risk; malignant breast neoplasm; mouse model; prevent; prostate carcinogenesis; response; soy; soy protein isolate; survivorship; valyl-valyl-valine; valylvaline

DESCRIPTION (provided by applicant): Soy consumption may prevent prostate cancer and be beneficial for patients with this cancer. However, there are contradictory data on the anticancer effects of the soy isoflavone genistein, which has antioxidant properties and can affect cell proliferation and apoptosis of cancer cells through multiple mechanisms, including estrogen receptor-¿ mediation. Genistein also affects the expression of the manganese superoxide dismutase (MnSOD) gene and polymorphisms in this gene are related to risk of prostate cancer. This proposal addresses the hypothesis that the proliferative or inhibitory effects of physiological concentrations of genistein on prostate cancer cells are dependent on their MnSOD genotype and ER-¿ status, as well as on oxidative stress levels. To test this hypothesis, we will determine how genistein acts on prostate cancer cells with different MnSOD variants and ER-¿ expression in a controlled oxidative stress environment with these Specific Aims: (1) Determine the influence of ER-¿ expression on the effects of physiological genistein concentrations on cell proliferation and apoptosis. Physiological concentrations of genistein will be used in controlled ROS environments in cells with specific MnSOD genotypes. (2) Determine the influence of MnSOD genotype on the effects of genistein on cell proliferation and apoptosis of prostate cancer cells expressing different MnSOD variants, while controlling their ER-¿ status and the ROS environment. (3) Determine the effects of genistein on prostate cancer cell proliferation and apoptosis at varying input levels of reactive oxygen species (O2.-), while controlling ER-¿ status and MnSOD genotype. The results of this proposal will provide preliminary data for an R01 application for further studies in animal models relevant to soy consumption in therapeutic and chemopreventive settings with a focus on non-linear dose-response relationships contrasting potential benefit with possible harm of genistein.

描述（由申请人提供）： 大豆消耗可能会预防前列腺癌，并对这种癌症患者有益。然而，存在有关大豆异黄酮染料蛋白酶的抗癌作用的矛盾数据，该染料具有抗氧化特性，可以通过包括雌激素受体 - 介导在内的多种机制来影响癌细胞的细胞增殖和凋亡。染料木黄酮还会影响锰超氧化物歧化酶（MNSOD）基因的表达，该基因中的多态性与前列腺癌的风险有关。该提议解决了以下假设：染料木黄酮物理浓度对前列腺癌细胞的增殖或抑制作用取决于其MNSOD基因型和ER-€的状态以及氧化应激水平。为了检验这一假设，我们将确定染料碱在具有不同的氧化应激环境中具有不同MNSOD变体和ER-ER-表达的前列腺癌细胞的作用，并具有这些特定目的：（1）确定ER-表达对物理染料碱浓度对细胞增殖和凋亡的影响的影响。染料木黄酮的生理浓度将用于具有特定MNSOD基因型的细胞的受控ROS环境中。 （2）确定MNSOD基因型对染料木黄酮对表达不同MNSOD变体细胞细胞增殖和凋亡的影响，同时控制其ER-€状态和ROS环境的影响。 （3）确定染料木黄酮对反应性氧的输入水平（O2.-）的影响，同时控制ER-€状态和MNSOD基因型，对前列腺癌细胞增殖和凋亡的影响。该提案的结果将为R01应用提供初步数据，以在与大豆消耗相关的动物模型和化学预防环境中有关的进一步研究，重点是非线性剂量 - 响应关系，将潜在的益处与可能的造成染色木币的危害相比。