Breast Cancer Prevention Using Bitter Melon as a Natural Product

使用苦瓜作为天然产品预防乳腺癌

基本信息

批准号：
9116142
负责人：
Ratna B. Ray
金额：
$ 16.48万
依托单位：
SAINT LOUIS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-09-01 至 2018-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9116142
关键词：
Adjuvant Adverse effects Affect Africa American Cancer Society Animal Model Anti-Inflammatory Agents Anti-inflammatory Applications Grants Asia Breast Cancer Cell Breast Cancer Model Breast Cancer Prevention Breast Cancer cell line Cancer Control Cancer Etiology Cancer cell line Cells Cessation of life Chemopreventive Agent Clinical Cyclin D1 Data Development Diabetes Mellitus Diet Disease Endocrine Equilibrium Event Folk Medicine Goals Growth Health Histopathology Hyperlipidemia Immune Immunity Immunomodulators Immunosuppressive Agents In Vitro Incidence Malignant Neoplasms Mammary Neoplasms Mediating Melons Momordica charantia Natural Killer Cells Natural Products Outcome Plant Extracts Pre-Clinical Model Prevention Preventive Primary Prevention Regulatory T-Lymphocyte Role Signal Pathway South America T-Lymphocyte TP53 gene Tissues Transgenic Animals Tumor Tissue United States Woman Work base cancer prevention cancer risk cell killing cell type cyclin B1 diabetic disorder prevention feeding immunoregulation implantation in vivo malignant breast neoplasm mortality neoplastic neoplastic cell novel novel strategies outcome forecast patient population pre-clinical prevent treatment strategy tumor tumor microenvironment

项目摘要

DESCRIPTION (provided by applicant): Breast cancer is the most common cancer among women in the United States. It is the second leading cause of cancer death in women. The American Cancer Society estimates about 232,670 new cases of invasive breast cancer in 2014 and ~ 40,000 women will die from breast cancer this year. Despite the use of adjuvant endocrine treatment, prognosis remains poor for a significant population of patients. One of the approaches to control cancer could be its prevention by diet, which inhibit one or more neoplastic events and reduce the cancer risk. Cancer prevention by the use of naturally occurring dietary substances is considered a practical approach to reduce the incidence of cancer. Bitter melon (Momordica charantia) is widely cultivated in Asia, Africa, and South America and extensively used in folk medicines as a remedy for diabetes. We have observed an anti-proliferative effect of bitter melon extract (BME) in a number of breast cancer cell lines in vitro. BME mediated breast cancer cell killing is associated with enhanced expression of p53, p21, and pChk1/2, and decreased expression of cyclin B1 and cyclin D1. More evidence support the importance of the tumor microenvironment (TME) in cancer development and progression where other cell types (such as immune cells) cross-talk with tumor cells. Naturally occurring anti-inflammatory or immunomodulatory plant extracts contribute to an anticancer effect by modulation of immune signaling pathways. However, the role of BME as an immunomodulator in breast cancer has not been studied. Based upon our in vitro data, we hypothesize that BME has chemopreventive activity against breast cancer growth by activating NK cell activity and inhibiting immunosuppressive T cell (Treg) function. In this R21 exploratory grant application, we will explore the preventive potential of BME against breast cancer and its novel mechanism as an immune modulator in the tumor microenvironment. Together, our proposed work will hold promise to advance our understanding of breast cancer disease prevention and may open up new avenues for additional treatment strategies.

描述（由适用提供）：乳腺癌是美国女性中最常见的癌症。这是女性癌症死亡的第二大原因。美国癌症协会估计，2014年约有232,670例新的侵入性乳腺癌病例，今年约有40,000名女性将死于乳腺癌。尽管使用了可调节的内分泌治疗，但对于大量患者来说，预后仍然很差。控制癌症的方法之一可能是饮食预防，饮食会抑制一个或多个肿瘤事件并降低癌症风险。通过使用天然饮食物质的使用被认为是降低癌症发生率的实际方法。苦瓜（Momordica Charantia）在亚洲，非洲和南美广泛种植，并广泛用于民间药物中，作为糖尿病的疗法。我们已经观察到在体外许多乳腺癌细胞系中苦瓜提取物（BME）的抗增殖作用。 BME介导的乳腺癌细胞杀伤与p53，p21和PCHK1/2的表达增强以及细胞周期蛋白B1和细胞周期蛋白D1的表达降低有关。更多证据支持肿瘤微环境（TME）在癌症发育和进展中的重要性，而其他细胞类型（例如免疫细胞）与肿瘤细胞进行了交叉。天然存在的抗炎或免疫调节植物提取物通过调节免疫信号途径有助于抗癌作用。但是，BME作为免疫调节剂在乳腺癌中的作用尚未研究。基于我们的体外数据，我们假设BME通过激活NK细胞活性并抑制免疫抑制性T细胞（TREG）功能，对乳腺癌的生长具有化学预防活性。在此R21探索性赠款应用中，我们将探讨BME抗乳腺癌及其作为肿瘤微环境中免疫调节剂的新型机制的预防潜力。我们提出的工作将共同有望提高我们对预防乳腺癌疾病的理解，并可能为其他治疗策略开辟新的途径。