Lupeol, A Novel Fuit and Vegetable Based Triterpene for Prostate Cancer

羽扇豆醇，一种治疗前列腺癌的新型水果和植物三萜

基本信息

批准号：
7321036
负责人：
Mohammad Saleem Bhat
金额：
$ 7.35万
依托单位：
UNIVERSITY OF WISCONSIN-MADISON
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-08-01 至 2009-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7321036
关键词：
Ablation Androgen Receptor Androgens Animal Model Apoptotic Appendix Cancer Etiology Cancer Patient Cause of Death Cells Cessation of life Chemoprevention Chemopreventive Agent Clinical Complex Condition Cultured Cells Cyclins DU145 Data Diagnosis Diet Distant Dose E-Cadherin Elderberry Federal Government Figs - dietary Fruit Goals Grapes Growth Harvest Hormones Human Implant In Vitro Inositol Invasive Legal patent Link Malignant neoplasm of prostate Mango - dietary Matrix Metalloproteinases Mediating Medicinal Plants Metastatic Prostate Cancer Molecular Monitor Mus NF-kappa B Neoplasm Metastasis Normal Cell Nude Mice Numbers Nutrient Olives - dietary Operative Surgical Procedures PTEN gene Pathway interactions Patients Phosphotransferases Play Preventive Property Prostate Prostatic Neoplasms Proteins Protocols documentation Publications Publishing Recurrence Refractory Resistance Role Signal Pathway Signal Transduction Site Strawberries Testing Therapeutic Therapeutic Agents Time Transcriptional Activation Triterpenes Tumor Volume Tumorigenicity Vascular Endothelial Growth Factors Vegetables Week Xenograft Model Xenograft procedure androgen independent prostate cancer base beta catenin cancer cell cancer therapy cell growth chemotherapeutic agent day fruits and vegetables implantation killings lupeol mRNA Expression men neoplastic cell novel novel therapeutics pre-clinical prevent receptor research study response subcutaneous tumor tumor growth

项目摘要

DESCRIPTION (provided by applicant): It is estimated that 234,460 new prostate cancer cases will be diagnosed and approximately 27,350 prostate cancer-related deaths are predicted in the US alone in the year 2006. Persistence of isolated cancer cells (even after surgery and androgen-ablation therapy), their proliferation, androgen-independence and invasion to distant sites is the major cause of deaths in human prostate cancer patients. Aberration in the levels and functioning of multiple proteins or molecular pathways including beta catenin, nuclear factor kappa B and phosphotidyl inositol 3 kinase /Akt signaling network, has been associated with the androgen-independence, proliferation, invasion and chemoresistance of prostate cancer cells. Since most of the chemotherapeutic agents generally target a specific protein or a molecular pathway, they most often fail to inhibit the growth of advanced prostate cancer in preclinical and clinical settings. Thus, it is important to identify novel agents with an ability to target multiple molecular pathways. It is increasingly appreciated that chemoprevention through diet-based natural agents could be an effective approach to prevent and treat prostate cancer in humans. Based on our published studies and preliminary data, we believe that Lupeol, a non-nutrient and non-toxic natural agent present in strawberry, grapes, mango, figs, olive and vegetables, could be an ideal chemopreventive and therapeutic agent with an ability to act on multiple molecular pathways. We hypothesize that Lupeol has the potential to kill highly aggressive and chemoresistant prostate cancer cells while sparing normal cells, inhibit their proliferation and invasion through the modulation of beta catenin, nuclear factor kappa B and phosphotidyl inositol 3 kinase /Akt signaling network. It is important to emphasize that, consistent with current NCI opinion, the term "chemoprevention" is used in its broadest sense in this application, i.e. in a partially therapeutic as well as purely preventive context. To achieve our goal, we propose two specific aims: (1) to investigate the anti-proliferative potential of Lupeol against androgen-independent prostate cancer cells, and to define its mechanism of action under cell culture conditions and (2) to investigate whether Lupeol possesses the chemopreventive and/or chemotherapeutic effects against the tumorigenicity of androgen-insensitive prostate cancer cells in an animal model. We believe that this application will be extremely valuable in providing a novel fruit and vegetable based agent for chemoprevention and possibly for treating prostate cancer

描述（由申请人提供）：据估计，2006 年，仅在美国，将诊断出 234,460 例新的前列腺癌病例，预计将有约 27,350 例前列腺癌相关死亡。孤立的癌细胞的持续存在（即使在手术和雄激素消融治疗之后）、它们的增殖、雄激素非依赖性和远处侵袭是人类前列腺癌患者死亡的主要原因。多种蛋白质或分子通路（包括β连环蛋白、核因子κB和磷脂酰肌醇3激酶/Akt信号网络）的水平和功能异常与前列腺癌细胞的雄激素非依赖性、增殖、侵袭和化疗耐药有关。由于大多数化疗药物通常针对特定蛋白质或分子途径，因此它们在临床前和临床环境中通常无法抑制晚期前列腺癌的生长。因此，识别能够靶向多种分子途径的新型药物非常重要。人们越来越认识到，通过基于饮食的天然药物进行化学预防可能是预防和治疗人类前列腺癌的有效方法。根据我们已发表的研究和初步数据，我们相信羽扇豆醇是一种存在于草莓、葡萄、芒果、无花果、橄榄和蔬菜中的非营养且无毒的天然物质，可能是一种理想的化学预防和治疗剂，能够作用于多种分子途径。我们假设羽扇豆醇有可能杀死高度侵袭性和化学耐药性的前列腺癌细胞，同时保留正常细胞，通过调节 β 连环蛋白、核因子 kappa B 和磷脂酰肌醇 3 激酶 /Akt 信号网络抑制其增殖和侵袭。需要强调的是，与目前 NCI 的观点一致，术语“化学预防”在本申请中以其最广泛的含义使用，即在部分治疗以及纯粹预防的背景下。为了实现我们的目标，我们提出了两个具体目标：（1）研究羽扇豆醇对雄激素非依赖性前列腺癌细胞的抗增殖潜力，并确定其在细胞培养条件下的作用机制；（2）研究羽扇豆醇是否在动物模型中对雄激素不敏感的前列腺癌细胞的致瘤性具有化学预防和/或化学治疗作用。我们相信，该应用对于提供一种新的基于水果和蔬菜的化学预防剂以及可能用于治疗前列腺癌非常有价值