Breast Cancer Prevention Using Bitter Melon as a Natural Product

 描述(申请人提供)：乳腺癌是美国女性中最常见的癌症。它是导致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例浸润性乳腺癌新病例，今年将有约40,000名女性死于乳腺癌。尽管使用了辅助内分泌治疗，但对于相当一部分患者来说，预后仍然很差。控制癌症的方法之一可能是通过饮食来预防癌症，饮食可以抑制一个或多个肿瘤事件，降低癌症风险。通过使用自然产生的饮食物质来预防癌症被认为是降低癌症发病率的一种实际方法。苦瓜(Momordica Charantia)在亚洲、非洲和南美洲广泛种植，并被广泛用作治疗糖尿病的民间药物。我们观察了苦瓜提取物(BME)在体外对一些乳腺癌细胞株的抗增殖作用。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。更多的证据支持肿瘤微环境(TME)在癌症发展和进展中的重要性，在这种情况下，其他类型的细胞(如免疫细胞)与肿瘤细胞相互作用。天然的抗炎或免疫调节植物提取物通过调节免疫信号通路来发挥抗癌作用。然而，BME作为免疫调节剂在乳腺癌中的作用尚未被研究。根据我们的体外数据，我们假设BME通过激活NK细胞活性和抑制免疫抑制T细胞(Treg)功能而具有抗乳腺癌生长的化学预防作用。在这次R21探索性拨款申请中，我们将探索BME预防乳腺癌的潜力及其在肿瘤微环境中作为免疫调节剂的新机制。总之，我们提议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.