Chemoprevention of Active Scutellaria baicalensis Fraction on Colon Cancer

描述(申请人提供)：结直肠癌是美国癌症相关死亡的主要原因。许多有效的抗癌药物已经从植物中开发出来，寻找新的草药来源来开发理想的化学预防仍然是推进结直肠癌治疗的关键步骤。候选人王宗智博士是芝加哥大学一位经验丰富的植物化学科学家。这份申请书描述了王博士的发展奖，他成功地实现了他的长期职业目标，即获得必要的技能，成为生物医学研究的独立研究员，专注于生物活性植物提取物/化合物治疗结直肠癌的疗效和机制。王博士的培训将侧重于提高他的生药学和植物成分新陈代谢知识，了解癌症病理生理学，熟练掌握生物统计学知识，并提高他的拨款撰写能力。顾问团队由芝加哥大学和伊利诺伊大学芝加哥分校的资深专家组成。初级导师袁春苏博士是芝加哥大学国立卫生研究院结直肠癌植物研究中心的首席研究员，他将密切指导王博士的培训和研究。初步数据显示，黄芩提取物(SBE)的不同部位对人结直肠癌细胞具有相反的作用。本研究的假设是，如果将黄芩提取物中的亲水性成分黄芩苷和黄芩素去除或转化为亲脂性成分，则提取物的抗癌作用将显著增强。本研究的目的是开发一种新的工艺来制备黄芩提取物富含苷元的部分(ARF)，以提高其抗癌活性，并阐明其潜在的作用机制。具体目标如下：目的1.SBE的鉴别、提取、分离及ARF的制备。目的2.评价SBE和ARF对结直肠癌的疗效及相关作用机制。目的3.进一步研究ARF诱导的细胞凋亡途径。这项拟议研究的数据将有可能推进癌症治疗方案，并改善结直肠癌患者的生活质量。在成功完成这一奖项后，王博士将为他的独立研究做好充分准备，他将利用植物成分进行更多基于药理的研究，以对抗结直肠癌。

DESCRIPTION (provided by applicant): Colorectal cancer is a leading cause of cancer-related death in the United States. Numerous effective anticancer drugs have been developed from botanicals, and identifying new herbal sources to develop ideal chemoprevention remains an essential step in advancing the treatment of colorectal cancer. The candidate, Dr. Chong-Zhi Wang, is an experienced phytochemical scientist at University of Chicago. This application describes a development award for Dr. Wang, to successfully achieve his long-term career goals of obtaining the skills necessary to become an independent investigator in biomedical research, concentrating on the efficacy and mechanism of bioactive botanical extracts/compounds for treating colorectal cancer. Training for Dr. Wang will focus on advancing his knowledge of pharmacognosy and metabolism of phytoconstituents, understanding cancer pathophysiology, becoming proficient in biostatistics knowledge, and improving his grant writing ability. The advisory team is composed of senior experts from the University of Chicago and University of Illinois at Chicago. The Primary Mentor Dr. Chun-Su Yuan, a Principal Investigator of NIH Center for Botanical Research on Colorectal Cancer at University of Chicago, will closely direct Dr. Wang's training and research. Preliminary data showed that the different fractions from Scutellaria baicalensis extract (SbE) had opposing effects on human colorectal cancer cells. The hypothesis of this study is that if the baicalin and scutellarein, hydrophilic constituents, are removed from S. baicalensis extract or transformed into lipophilic constituents, the anticancer effects of the extract will increase significantly. The purpose of the research is to develop a new process for preparing an aglycon-rich fraction (ARF) of S. baicalensis extract in improving its anticancer activities and to elucidate the underlying mechanisms. The specific aims are as follows: Aim 1. Authentication, extraction and isolation of SbE and preparation of ARF. Aim 2. Evaluation of the effects of SbE and ARF on colorectal cancer and related mechanisms of action. Aim 3. Further investigation of ARF-induced apoptotic pathways. Data from this proposed study will have the potential to advance cancer treatment regimens, and improve the quality of life for patients suffering from colorectal cancer. Upon successful completion of this award, Dr. Wang will be fully prepared for his independent investigation of additional pharmacologically based studies using phytoconstituents against colorectal cancer.