Chemoprevention of Active Scutellaria baicalensis Fraction on Colon Cancer

描述（由申请人提供）：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，并且确定新的草药来源以开发理想的化学预防仍然是推进结直肠癌治疗的重要步骤。候选人王崇智博士是芝加哥大学经验丰富的植物化学科学家。该申请描述了王博士的发展奖，以成功实现他的长期职业目标，即获得成为生物医学研究独立研究者所需的技能，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。对王博士的培训将侧重于提高他的生药学和植物成分代谢知识，了解癌症病理生理学，精通生物统计学知识，并提高他的赠款写作能力。顾问小组由来自芝加哥大学和伊利诺伊大学芝加哥分校的资深专家组成。主要导师袁春素博士是芝加哥大学NIH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。初步数据表明，黄芩提取物（SbE）的不同组分对人结直肠癌细胞具有相反的作用。本研究假设，如果从S.黄芩提取物或转化为亲脂性成分，提取物的抗癌作用将显著增加。本研究的目的是开发一种新的制备S.提高黄芩提取物的抗肿瘤活性，并阐明其作用机制。具体目标如下：目标1。SbE的鉴定、提取、分离及ARF的制备。目标2.评价SbE和ARF对结直肠癌的作用及其相关作用机制。目标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。在成功完成该奖项后，王博士将为他的独立调查做好充分的准备，这些调查基于植物成分对结直肠癌的其他研究。 公共卫生相关性：结直肠癌是美国癌症相关死亡的主要原因。虽然在开发针对这种癌症的有效治疗策略方面取得了进展，但化疗仍然受到严重不良反应和剂量限制性毒性的限制。本项目将以中草药黄芩为原料，采用新的提取工艺制备黄芩有效部位，并评价黄芩有效部位对大肠癌的抗癌作用。

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. PUBLIC HEALTH RELEVANCE: Colorectal cancer is a leading cause of cancer related death in the United States. While advances have been made in developing effective treatment strategies for this cancer, chemotherapies are still limited by severe adverse effects and dose-limiting toxicity. This Project will use Scutellaria baicalensis, a Chinese herb medicine, with a new extract process to produce an active fraction, and evaluate the active fraction's anticancer effects on colorectal cancer.