Enhancement of Academic Research at Southern University Baton Rouge

加强巴吞鲁日南方大学的学术研究

• 批准号: 8626515
• 负责人: Wesley George Gray
• 金额: $ 36.22万
• 依托单位: SOUTHERN UNIV A&M COL BATON ROUGE
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-01 至 2017-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8626515
• 关键词: Academic Research Enhancement Awards; Affect; Androgen Receptor; Androgens; Apoptosis; Apoptotic; Biochemistry; Biological; Biological Factors; Biological Process; Biology; Biomedical Research; Cancerous; Cell Cycle; Cell Death; Cell Line; Cell model; Cells; Chemicals; Chemistry; Chemopreventive Agent; Collaborations; DU145; Data; Dependency; Development; Diet; Dietary Fiber; Disease; Ensure; Environment; Estrogens; Ethers; Fabaceae; Gene Expression; Generations; Genes; Genus Cola; Goals; Grant; Health; Herbal Medicine; High Pressure Liquid Chromatography; Hormonal; Hormones; In Vitro; Induction of Apoptosis; Jamaica; Knowledge; LNCaP; Malignant Neoplasms; Malignant neoplasm of prostate; Medical; Medicinal Tea; Mentors; Mitochondria; Modality; Modeling; Molecular; Molecular Profiling; NMR Spectroscopy; Nuts; Plant Roots; Preventive; Principal Investigator; Property; Prostate; Public Health; Reagent; Regimen; Reporting; Research; Research Project Grants; Scientist; Signal Pathway; Signal Transduction; Structure; System; Testing; Tissues; Training; Transformed Cell Line; United States; Universities; cancer type; experience; graduate student; improved; insight; interest; neoplastic cell; novel; novel therapeutic intervention; novel therapeutics; programs; prostate cancer cell; protein expression; public health relevance; receptor; soy; success; tool; tumor; undergraduate student

DESCRIPTION (provided by applicant): Biologically active, non-steroidal, androgenic and estrogenic agents are found primarily in soy products, legumes, and whole grains, as well as in medicinal teas and roots. Kola acuminate, also known as Bizzy nut to the Ettu people of Jamaica, is a "cure-all" herbal medicine that reportedly affects a variety of biological processes, many of which are directly or indirectly modulated by hormones. Available ethnobotanical information suggests that Kola acuminate may contain bioactive chemicals that possess estrogenic and androgenic properties. Anecdotal reports suggest that Bizzy nut may be useful for a number of medical purposes. Given the hormonal dependency of some of these biological activities, it is possible that non-steroidal androgen present in the Bizzy nut is responsible for he medicinal value attributed to it. The key to an agent's success, as a chemo preventive agent in the prostate and other types of cancer, relies on the agent's ability to induce tumor cell death in a tissue-dependent and receptor-dependent manner. Naturally occurring agents that induce apoptosis in prostate cells in an AR-dependent manner would signal a new generation of prostate-specific, chemo preventive agents. The goal of this research project is to test the hypothesis that ether extract of Bizzy (Biz-2) modulates prostate function in a predictable manner. Thus, the overall objective of this revised application remains the same, namely demonstrating that the Kola acuminate (Bizzy Nut) extract contains bioactive compounds capable of functioning as chemo preventive agents against prostate cancer. The initial focus of this application is to isolated and identify the bioactive compounds found in the Biz-2Fr.3 fraction of Bizzy Nut and demonstrate, In vitro, its anti- cancer/chemo preventive potential using three prostate cancer cell models. To this end, two Specific Aims were developed. Aim 1: is to isolate and characterize the bioactive compounds in Bizzy nut extract associated with its anti-cancer properties in prostate cells. The goals of this Aim are to (1) Isolate and characterize the bioactive components of Biz-two by preparative HPLC; (2) elucidate the structure of the compounds in Biz-2Fr.3 using a combination of UV-Vis, NMR spectroscopy, LC-MS; and (3) Demonstrate the anti-cancer capability of the bioactive substances in Biz-2Fr.3. Aim 2: is to Identify the Biz-2Fr.3-induced apoptotic signaling pathways and determine the molecular mechanisms by which Biz-2FR.3 induces apoptosis in prostate cells. The goals of this Aim are to; (1) determine the mechanism of Biz-2Fr.3 anti-tumor activity using change in cell cycle distribution and protein expression profiling of cyclines. (2) Determine the involvement of mitochondria in Biz-2Fr.3 induction of apoptosis in normal and cancerous prostate cells using three prostate cell lines, the AR+ LNCaP, the AR- DU145 cells and RWP-1a normal, transformed cell line. We are well prepared to undertake the proposed research because of our experience with the experimental systems (see preliminary results) and the unique team of expert scientists in chemistry, biology and biochemistry as well as our collaborators and mentors from the LSU Chemistry and SUBR chemistry who are involved with the project. We have developed and assembled a set of tools, critical reagents and cell lines that will ensure success of this application. In addition, the proposed study is strongly supported by our preliminary data that validate the hypotheses that guide the proposed research. Finally, the combination of the assembled expertise, adequate facilities, strong collaborations and institutional support will allow us to conduct this study in a research environment that is conducive to its success.

描述（由申请人提供）：生物活性、非甾体、雄激素和雌激素制剂主要存在于大豆制品、豆类和全谷物以及药用茶和根中。科拉acuminate，也被称为Bizzy坚果牙买加的Ettu人，是一种“包治百病”的草药，据报道，影响各种生物过程， 其中许多是直接或间接受激素调节的。现有的民族植物学信息表明，可乐果可能含有具有雌激素和雄激素特性的生物活性化学物质。传闻中的报告表明，Bizzy nut可能用于许多医疗目的。鉴于其中一些生物活性对激素的依赖性，Bizzy nut中存在的非甾体雄激素可能是其药用价值的原因。作为前列腺和其他类型癌症的化疗预防剂，药物成功的关键依赖于该药物诱导肿瘤细胞死亡的能力 组织依赖性和受体依赖性的方式。以AR依赖性方式诱导前列腺细胞凋亡的天然药物将成为新一代前列腺特异性化疗预防药物的信号。本研究项目的目的是检验Bizzy（Biz-2）乙醚提取物以可预测的方式调节前列腺功能的假设。因此，该修订申请的总体目标保持不变，即证明Kola acuminate（Bizzy Nut）提取物含有能够作为针对前列腺癌的化学预防剂起作用的生物活性化合物。本申请的最初重点是分离和鉴定在Bizzy Nut的Biz-2Fr.3级分中发现的生物活性化合物，并使用三种前列腺癌细胞模型在体外证明其抗癌/化学预防潜力。为此，制定了两个具体目标。目的1：分离和表征Bizzy nut提取物中与其在前列腺细胞中的抗癌特性相关的生物活性化合物。本目标的目的是（1）通过制备型HPLC分离和表征Biz-two的生物活性组分;（2）使用UV-Vis，NMR光谱，LC-MS的组合阐明Biz-2Fr.3中化合物的结构;和（3）证明Biz-2Fr.3中生物活性物质的抗癌能力。目标二：目的是鉴定Biz-2FR.3诱导的凋亡信号通路，并确定Biz-2FR.3诱导前列腺细胞凋亡的分子机制。本研究的目的是：（1）使用细胞周期分布和细胞周期蛋白表达谱的变化确定Biz-2Fr.3抗肿瘤活性的机制。(2)使用三种前列腺细胞系，AR+ LNCaP、AR-DU 145细胞和RWP-1a正常转化细胞系，确定线粒体参与Biz-2Fr.3诱导正常和癌性前列腺细胞凋亡。我们已经做好充分准备进行拟议的研究，因为我们的经验与实验系统（见初步结果）和专家科学家在化学，生物学和生物化学的独特团队，以及我们的合作者和导师从路易斯安那州立大学化学和SUBR化学谁是参与该项目。我们已经开发并组装了一套工具、关键试剂和细胞系，以确保这一应用的成功。此外，我们的初步数据也有力地支持了这项研究，这些数据验证了指导这项研究的假设。最后，汇集的专业知识，充足的设施，强有力的合作和机构支持的结合将使我们能够在有利于其成功的研究环境中进行这项研究。