Anticancer Potential of Black Cohosh on Breast Cancer

描述(由申请人提供)：我的意图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。我的目标是开始在大学或研究机构从事富有成效的研究和教学事业，这将导致新型抗癌疗法和化学预防药物的开发和临床应用。该项目的重点将是草药的机制研究，特别是黑升麻，在体外和体内对癌症的研究。实现这一目标的理想导师是I.伯纳德·温斯坦博士，他是癌症发生的分子方面的专家，理想的环境是哥伦比亚大学内科和外科医学院。黑升麻Actaea racemosa L.(=Cimicifuga racemosa)是毛豆科(Ranunculaceae)的一种北美多年生植物，用于各种女性的健康保健。该项目的总体目标是确定黑升麻是否含有最终可能在预防或治疗乳腺癌方面有用的成分。事实上，我们的初步实验表明，黑升麻提取物抑制了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单独和与化疗药物结合，检查它们对控制细胞生长、细胞周期、细胞凋亡以及ER和HER-2受体功能的特定分子的功能的影响。Western印迹分析将检测对细胞周期蛋白D1相关蛋白表达的可能影响。荧光素酶报告分析将监测对核因子-kB、fos、myc、jun和PPAR-g转录的影响。分析化学技术将被用来识别可能调节这些效应的新化合物。为了确定化合物治疗人类的有效性，我们将检测黑升麻提取物对裸鼠体内人乳腺癌细胞系异种移植的影响。这项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.