Anticancer Potential of Black Cohosh on Breast Cancer

描述（由申请人提供）：我的目的是将我在微生物学和病毒肿瘤学方面的背景与对癌症和草药的新兴趣结合起来。我的目标是在大学或研究机构开展富有成效的研究和教学工作，这将导致新型抗癌疗法和化学预防剂的开发和临床应用。这个项目的重点将是草药，特别是黑升麻，在体外和体内对癌症的机制研究。要做到这一点，理想的导师是I. Bernard Weinstein博士，他是致癌分子方面的专家，理想的环境是哥伦比亚大学内外科医生学院。黑升麻，Actaea racemosa L. (= Cimicifuga racemosa)，是北美毛茛科（毛茛科）的多年生植物，用于各种女性健康状况。该项目的总体目标是确定黑升麻是否含有可能最终用于预防或治疗乳腺癌的成分。事实上，我们的初步实验表明，黑升麻提取物抑制人类乳腺癌细胞的生长。我们将测定黑升麻的药代动力学。部分纯化的提取物和特定的化学物质将被检查它们单独或与化疗药物联合对控制细胞生长、细胞周期、细胞凋亡和内质网和Her-2受体功能的特定分子的功能的影响。Western blot分析将检查对cyclin D1相关蛋白表达的可能影响。荧光素酶报告基因检测将用于监测对NF-kB、fos、myc、jun和PPAR-g转录的影响。分析化学技术将用于鉴定可能介导这些作用的新化合物。为了确定化合物治疗人类的功效，我们将研究黑升麻提取物对胸腺小鼠人类乳腺癌细胞系异种移植的影响。这个研究项目可以确定乳腺癌预防和治疗的新方法。

DESCRIPTION (provided by applicant): My intent is to combine my background in microbiology and viral oncology with newer interests in cancer and herbal medicines. My objective is to initiate a productive career in research and teaching at a university or research institute that will lead to the development and clinical use of novel anticancer therapies and chemopreventive agents. The focus of this project will be mechanistic studies of herbal medicines, in particular black cohosh, on cancer in vitro and in vivo. The ideal mentor to accomplish this is Dr. I. Bernard Weinstein, who is an expert on molecular aspects of carcinogenesis and the ideal environment is Columbia University College of Physicians and Surgeons. Black cohosh, Actaea racemosa L. (= Cimicifuga racemosa), is a North American perennial in the buttercup family (Ranunculaceae) used for various women's health conditions. The overall objective of this project is to determine whether black cohosh contains components that may eventually be useful in the prevention or treatment of breast cancer. Indeed, our preliminary experiments indicate that black cohosh extracts inhibit the growth of human breast cancer cells. We will determine the pharmacokinetics of black cohosh. Partially purified extracts and specific chemicals will be examined for their effects, alone and in combination with chemotherapy agents, on the function of specific molecules that control cell growth, the cell cycle, apoptosis and the function of the ER and Her-2 receptor. Western blot analysis will be performed to examine possible effects on the expression of cyclin D1 related proteins. Luciferase reporter assays will be done to monitor effects on the transcription of NF-kB, fos, myc, jun and PPAR-g. Analytic chemical techniques will be used to identify novel compounds that might mediate these effects. To ascertain the efficacy of the compounds to treat humans, we will examine effects of an extract of black cohosh on xenografts of human breast cancer cell lines in athymic mice. This research project could identify new approaches to breast cancer prevention and therapy.