Breast Cancer Prevention Using Bitter Melon as a Natural Product

 描述（由申请人提供）：乳腺癌是美国女性中最常见的癌症。它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例新发浸润性乳腺癌病例，今年将有约40，000名女性死于乳腺癌。尽管使用辅助内分泌治疗，预后仍然很差的一个显着的患者群体。控制癌症的方法之一可能是通过饮食进行预防，从而抑制一种或多种肿瘤事件并降低癌症风险。通过使用天然存在的膳食物质来预防癌症被认为是降低癌症发病率的实用方法。苦瓜（苦瓜）广泛种植于亚洲、非洲和南美洲，并广泛用于民间医药作为治疗糖尿病的药物。我们已经观察到苦瓜提取物（BME）在体外的乳腺癌细胞系中的抗增殖作用。BME介导的乳腺癌细胞杀伤与p53、p21和pChk 1/2的表达增强以及细胞周期蛋白B1和细胞周期蛋白D1的表达降低相关。更多证据支持肿瘤微环境（TME）在癌症发展和进展中的重要性，其中其他细胞类型（例如免疫细胞）与肿瘤细胞发生串扰。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传导途径有助于抗癌作用。然而，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细胞活性和抑制免疫抑制性T细胞（Treg）功能对乳腺癌生长具有化学预防活性。在这项R21探索性资助申请中，我们将探索BME对乳腺癌的预防潜力及其作为肿瘤微环境中免疫调节剂的新机制。总之，我们提出的工作将有望促进我们对乳腺癌疾病预防的理解，并可能为其他治疗策略开辟新的途径。

 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.