Cancer Prevention by West African Medicinal Plants

西非药用植物预防癌症

基本信息

批准号：
7625387
负责人：
MICHAEL WARGOVICH
金额：
$ 13.61万
依托单位：
MEDICAL UNIVERSITY OF SOUTH CAROLINA
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-02-03 至 2010-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7625387
关键词：
Adansonia Adverse effects Africa African Anti-Inflammatory Agents Anti-inflammatory Apoptosis Apoptotic Automobile Driving Azadirachta Biological Biological Assay Biological Factors Botanicals Caspase Chemoprevention Chemopreventive Agent Colitis Collaborations Colon Colon Carcinoma Complementary and alternative medicine Complex Condition Cytostatics Detection Development Disease Dose Event Fever Flow Cytometry Fractionation Future Gastritis General Population Genus Cola Goals Grant Guinea Healed Hemorrhage Human Indigenous Indigenous Medicine Induction of Apoptosis Inflammation Inflammatory Knowledge Lead Link Malignant Neoplasms Measures Mediating Medicinal Plants Methodology Methods Modems Non-Steroidal Anti-Inflammatory Agents Numbers Ocimum basilicum Organ PTGS2 gene Pain Pathway interactions Pharmaceutical Preparations Planet Mars Plant Extracts Plants Preventive Process Prostaglandin-Endoperoxide Synthase Prostaglandins Protein Isoforms Proteins Public Health Quality Control RNA Range Research Research Personnel Risk Role Rural Safety Scientist Senegal Signal Pathway Signal Transduction Source Standards of Weights and Measures Stomach Carcinoma Stroke TdT-Mediated dUTP Nick End Labeling Assay Testing Trees Ulcer cancer chemoprevention cancer prevention cancer risk chemical fingerprinting colon cancer cell line cyclooxygenase 1 cyclooxygenase 2 cytotoxic cytotoxicity forest healing in vitro Bioassay inhibitor/antagonist malignant stomach neoplasm mortality novel programs protein expression response tumor

项目摘要

DESCRIPTION (provided by applicant): The overall goal of this project is to discover novel, anti-inflammatory compounds from medicinal plants native to West Africa. The broad long-term objective is to establish a role for this unexploited source of natural products for future chemoprevention applications for colon and other cancers. The inflammatory process appears to be an important biological undercurrent in several common human cancers. Many inflammatory disease states increase the risk for cancer in a particular organ; gastritis for stomach cancer, and colitis for colon cancer are examples. Habitual use of non-steroidal anti-inflammatory drugs (NSAIDS) appears to reduce the risk for several types of human cancer, most notably, colon cancer. Yet, long-term use of NSAIDS in cancer chemoprevention is a complex issue, marred by major side effects including prolonged bleeding, ulceration, and risk of stroke; some of these events occur in even with the advent of selective COX-2 inhibitors. West Africa is rich in indigenous medicinal practices including knowledge and use of botanicals with wide anti-inflammatory effects. The hypothesis to be tested is that native medicinal plants from West Africa used traditionally for relief of pain, fever, and inflammation interacts to inhibit cyclooxgenases 1 and 2, implicated in corrupted cell signaling pathways co-opted by human tumors. We postulate that these African botanicals will have NSAID-like effects and will inhibit COX pathways involved in colon cancer, but will have the advantage of a wider margin of safety. The specific aims of this project are: 1) To develop chemical fingerprints of five West African plant extracts (neem tree, baobab tree, Senegal mahogany, African basil, and kinkirissi bush) as initial quality control measures and a starting panel for future fractionation and isolation of active principles 2). to determine if extracts (decoctions) of 5 West African medicinal plants have potential cytostatic or cytotoxic effects on a range of colon cancer cell lines differing in COX expression levels; 3) to determine whether extracts of African medicinal plants inhibit COX-1 and COX- 2 isoforms in colon cancer cell lines; and, 4) to determine if COX-dependent or independent pathways are involved in induction of apoptosis in colon cancer cell lines by the African botanicals selected for study. The methodologies used are RNA and protein expression assays for COX-1 and COX-2, standard dose response cytotoxicity assays using human colon cancer cell lines, and flow cytometry mediated detection of apoptosis and apoptotic proteins. The long-term goal of this project is to establish a biologically-driven fractionization program to further characterize active inhibitors detected in active African medicinal plants. We expect that having access to this unique source of bioactive natural products, combined with the use of both conventional and functional in vitro bioassays will lead to discovery of new chemopreventive agents which can be ultimately developed into clinically effective agents. We have unique access to actual plants with purported anti-inflammatory activity used by actual traditional healers in West Africa.

描述（由申请人提供）：该项目的总体目标是发现来自西非原产的药用植物的新颖的抗炎化合物。广泛的长期目标是为这种未来的天然产品来确立对结肠和其他癌症的未来化学预防应用的作用。在几种常见的人类癌症中，炎症过程似乎是重要的生物潜流。许多炎症性疾病状态增加了特定器官中癌症的风险。胃炎治疗胃癌，结肠癌的结肠炎就是例子。习惯使用非甾体类抗炎药（NSAID）似乎降低了几种类型的人类癌症的风险，最值得注意的是结肠癌。然而，长期使用NSAID在癌症化学预防中是一个复杂的问题，受到重大副作用的破坏，包括长时间出血，溃疡和中风的风险；这些事件中的一些发生在选择性COX-2抑制剂的出现。西非拥有丰富的土著药用实践，包括具有广泛抗炎作用的植物学知识和使用。要检验的假设是，来自西非的天然药用植物传统上用于缓解疼痛，发烧和炎症相互作用以抑制环氧酶1和2，这与人类肿瘤相互配置的损坏的细胞信号通路有关。我们假设这些非洲植物会具有类似NSAID的作用，并会抑制与结肠癌有关的COX途径，但将具有更大安全余量的优势。该项目的具体目的是：1）开发五种西非植物提取物的化学指纹（Neem Tree，Baobab Tree，塞内加尔Mahogany，非洲罗勒和Kinkirissi Bush）作为初始质量控制措施，以及用于未来分馏和分馏的起点措施主动原理的隔离2）。确定5种西非药用植物的提取物（腐烂）是否对COX表达水平不同的一系列结肠癌细胞系具有潜在的细胞抑制或细胞毒性作用； 3）确定非洲药物植物的提取物是否会抑制结肠癌细胞系中的Cox-1和Cox-2同工型；，4）确定选择研究的非洲植物学物质是否涉及Cox依赖性或独立的途径在结肠癌细胞系中凋亡。使用的方法是用于COX-1和COX-2的RNA和蛋白质表达测定，使用人结肠癌细胞系的标准剂量反应细胞毒性测定，以及流式细胞术介导的凋亡和凋亡蛋白的检测。该项目的长期目标是建立一个以生物学驱动的分馏计划，以进一步表征活跃的非洲药用植物中检测到的活跃抑制剂。我们预计，使用这种独特的生物活性天然产品来源，再加上常规和功能性生物测定的使用将导致发现新的化学预防剂，最终可以发展为临床上有效的药物。我们可以独特地使用西非实际传统治疗师使用的抗炎活动的实际植物。

项目成果

期刊论文数量（3）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Anticancer activity of limonoid from Khaya senegalensis.

Khaya senegalensis 柠檬苦素的抗癌活性。

DOI：
10.1002/ptr.2148
发表时间：
2007
期刊：
Phytotherapy research : PTR
影响因子：
0
作者：
Zhang,Huaping;Wang,Xi;Chen,Feng;Androulakis,XiaoM;Wargovich,MichaelJ
通讯作者：
Wargovich,MichaelJ

Chemopreventive effects of Khaya senegalensis bark extract on human colorectal cancer.

塞内加尔卡亚树皮提取物对人类结直肠癌的化学预防作用。

DOI：
发表时间：
2006
期刊：
Anticancer research.
影响因子：
0
作者：
Androulakis,XiaoM;Muga,StephanieJ;Chen,Feng;Koita,Youssouf;Toure,Boubacar;Wargovich,MichaelJ
通讯作者：
Wargovich,MichaelJ