Natural Agent in Prevention of Prostate Cancer

预防前列腺癌的天然药物

基本信息

批准号：
8956789
负责人：
Sanjeev Shukla
金额：
$ 17.24万
依托单位：
CASE WESTERN RESERVE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-07-01 至 2017-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8956789
关键词：
70-kDa Ribosomal Protein S6 Kinases Ablation Adverse effects Anti-Allergic Agents Anti-Infective Agents Anti-Inflammatory Agents Anti-inflammatory Antioxidants Apoptosis Applications Grants Binding Bioavailable Bioflavonoid Biological Models Buckwheat CDK2 gene CDK4 gene Cancer Etiology Cancer Patient Catalytic Domain Cell Cycle Regulation Cell Proliferation Cell Survival Cell-Cell Adhesion Cells Cessation of life Chemopreventive Agent Citrus Fruit Clinical Colon Carcinoma Complex Control Groups Cyclin D1 Cyclin E DU145 Data Disease Embryo Epithelial Epithelial Cells Event FOS gene Feedback Fibroblasts Flavanol Goals Growth Growth Factor Human Image Implant In Vitro Inhibition of Apoptosis Insulin-Like Growth Factor I Interleukin-6 Knock-out LNCaP MAP Kinase Gene MAPK3 gene Malignant neoplasm of ovary Malignant neoplasm of prostate Mesenchymal Messenger RNA Monitor Mus Neoplasm Metastasis Normal Cell Nude Mice PC3 cell line Pathway interactions Patients Phosphorylation Phosphotransferases Plant Preparations Plant Sources Plants Play Preventive Property Prostate Protein Kinase C Proteins Proto-Oncogene Proteins c-akt Public Health Raptors Reporting Rodent Role Series Signal Transduction Signaling Molecule Sirolimus Stream Tacrolimus Binding Protein 1A Testing Translations Tumor Promotion United States WI 38 cell Work bcl-1 Genes c-myc Genes cell growth cell motility cell transformation clinically relevant deguelin effective therapy high risk in vivo in vivo Model inhibitor/antagonist mRNA Expression mTOR protein male malignant breast neoplasm men mouse model overexpression permanent cell line prevent prostate cancer cell prostate cancer cell line prostate cancer model prostate cancer prevention protective effect protein complex protein expression public health relevance tumor tumor growth tumor progression

项目摘要

DESCRIPTION (provided by applicant): The proposed study will determine the chemo-preventive potential of diosmetin, a natural plant flavanol, in regulating Rictor; the core constituent and critical protein in the function of mTORC2 (rapamycin- insensitive) protein complex to prevent prostate cancer progression. The role of Rictor has been reported in colon, breast and ovarian cancers. Circulating growth factors phosphorylates Rictor protein at Thr-1135 in prostate cancer cells, moreover, increased presence of rictor results in series of events including phosphorylation of PKCa and Akt molecules. Both these molecules play significant role in cell survival, cell adhesion, cell transformation and cell cycle regulation. It has been demonstrated that rapamycin, the known inhibitor of mTOR kinase pathway has no inhibitory effect on Rictor (mTORC2 main component). The urgent need is to identify an effective agent that can regulate Rictor and its associated events PKCa and Akt to prevent prostate cancer progression. Diosmetin has anti- inflammatory, anti-oxidants and anticancer effects. The proposed study will explore the preventive role of diosmetin in targeting Rictor, its phosphorylation and also its associated signaling events in prostate cancer. The in vitro and in vivo studies will determine whether diosmetin has potential to inhibit Rictor, its phosphorylation, and additionally maintain rictor's presence to regulate kinase activities of PKCa and Akt at appropriate level, thereby resulting in reduced prostate cancer cell proliferation and tumor progression. Our long term goal is to develop diosmetin as safe and an effective chemopreventive agent for prostate cancer and to understand the role of Rictor in prostate cancer progression. Public Health Significance: There is an immediate need for an effective and clinically relevant strategy to inhibit prostate cancer, with minimal side-effects. Hereby using a natural agent from citrus fruits and herbal preparations, the potential of diosmetin will be tested against prostate cancer. Since prostate cancer is the second largest killer in the United States males, reducing deaths from this deadly form of disease is urgently needed.

描述（由适用提供）：拟议的研究将确定天然植物黄酮醇的化学预防潜力在调节中； MTORC2（雷帕霉素不敏感的）蛋白质复合物功能中的核心成分和关键蛋白质可预防前列腺癌的进展。 Richtor的作用已在结肠，乳腺癌和卵巢癌中报道。循环生长因子在前列腺癌细胞中THR-1135处的Richtor蛋白磷酸化，此外，Rictor的存在增加导致一系列事件，包括PKCA和AKT分子的磷酸化。这两个分子在细胞存活，细胞粘合剂，细胞转化和细胞周期调节中都起着重要作用。已经证明雷帕霉素是已知的MTOR激酶途径的抑制剂，对Richtor（MTORC2主成分）没有抑制作用。迫切需要的是确定可以调节Richtor及其相关事件PKCA和AKT的有效药物，以防止前列腺癌的进展。 Diosmemetin具有抗炎，抗氧化剂和抗气作用。拟议的研究将探索二米素在靶向Richtor，其磷酸化及其相关信号事件中的预防作用。体外和体内研究将确定二米素是否有可能抑制Richtor的磷酸化，即并在适当水平上保持Rictor的存在以调节PKCA和AKT的激酶活性，从而导致前列腺癌细胞的增殖和肿瘤进展减少。我们的长期目标是将二甲米素开发为前列腺癌的安全和有效的化学预防剂，并了解Rictor在前列腺癌进展中的作用。公共卫生的意义：立即需要采取有效且与临床相关的策略来抑制前列腺癌，并具有最小的副作用。特此使用柑橘类水果和草药制剂的天然剂，将测试二米素的潜力针对前列腺癌。由于前列腺癌是美国男性的第二大杀手，因此迫切需要减少这种致命的疾病形式的死亡。