Ginseng and its Constituents in Complementary Breast Cancer Therapy

描述(申请人提供)：人参是一种最畅销的草药补充剂，据称可以增强活力和改善健康，因此被癌症患者用作补充疗法。有报道称，人参的使用可能与乳腺癌患者的生存和生活质量的提高有关。在我们的初步数据中，我们证明了人参在体外增加了化疗药物阿霉素对乳腺癌细胞的抗癌效果，在体内增加了对肿瘤生长的抑制作用，并进一步防止了与阿霉素治疗相关的体重减轻。人参含有30多种不同的人参皂苷和多糖成分，被认为是人参根中的主要生物活性成分。我们提供了人参多糖刺激天然免疫系统和诱导巨噬细胞产生增加细胞因子释放的初步证据。反过来，人参皂苷可能直接作用于抑制癌细胞的增殖。我们利用培养的人乳腺癌MCF-7细胞进行的初步研究表明，细胞因子和人参皂苷可能共同作用于人参发挥抗癌作用的能力。剩下的是在活体模型中测试这些发现，并确定人参成分如何在阿霉素治疗期间对人参的补充有效性做出贡献。首先，将人乳腺癌MCF-7细胞接种到雌性裸鼠体内，观察补充人参对阿霉素抑制肿瘤生长和诱导全身毒性作用的影响。我们将利用两种治疗范例来模拟乳腺癌确诊后立即开始服用人参的个体(化疗前)或化疗开始时开始服用人参的个体。在研究结束时，将分析肿瘤组织的增殖和凋亡指数，血液激活先天免疫反应和全身毒性，以及心脏组织将分析与阿霉素治疗相关的心脏毒性。最后，将用人参皂苷和/或细胞因子处理人乳腺上皮细胞和乳腺癌细胞株，以确定可能导致人参诱导对阿霉素治疗增敏的信号和凋亡途径。我们假设活性人参成分将通过不同的作用机制协同作用，以最大限度地提高人参的安全性和补充有效性。这些数据将为卫生保健专业人员和公众提供关于人参及其成分丰富的提取物在补充乳腺癌治疗中的使用的循证信息的第一步。。 公共卫生相关性：这项R21赠款项目将确定人参皂苷和人参多糖成分在阿霉素治疗裸鼠乳腺癌模型中如何有助于人参的互补有效性；其次，解决人参成分的作用机制。我们的假设是，这些生物活性人参成分通过不同的作用机制共同作用，以最大限度地提高人参的安全性和补充有效性。这些数据将为卫生保健专业人员和公众提供关于人参及其成分丰富的提取物在补充乳腺癌治疗中的使用的循证信息的第一步。

DESCRIPTION (provided by applicant): Ginseng is a top-selling herbal supplement that is purported to increase vitality and improve health and, consequently, is used as a complementary therapy by cancer patients. There are some reports that ginseng use may be associated with increased survival and quality of life in breast cancer patients. In our preliminary data, we demonstrate that ginseng increases the anti-cancer efficacy of the chemotherapeutic doxorubicin on breast cancer cells in vitro and on tumor growth in vivo, and further prevents the weight loss associated with doxorubicin treatment. Ginseng contains over 30 different ginsenosides and polysaccharide components and these are considered the major bioactive constituents in the ginseng root. We provide preliminary evidence that ginseng polysaccharides stimulate the innate immune system and induce macrophages to produce increased cytokine release. In turn, the ginsenosides may act directly to inhibit cancer cell proliferation. Our preliminary studies using cultured human breast cancer MCF-7 cells show that together the cytokines and ginsenosides may be responsible for the ability of ginseng to exert anti-cancer effects. What remains is to test these findings in an in vivo model and determine how ginseng's constituents contribute to the complementary effectiveness of ginseng during doxorubicin treatment. First, female nude mice will be inoculated with human breast cancer MCF-7 cells and the effects of supplemental ginseng on the ability of doxorubicin to prevent tumor growth and induce systemic toxicity will be measured. We will utilize two treatment paradigms that are designed to simulate the individual who starts taking ginseng as soon as the breast cancer is diagnosed (pre-chemotherapy), or the individual who starts taking ginseng when chemotherapy is initiated. At the end of the study, tumor tissues will be analyzed for proliferation and apoptotic indices, blood for activation of innate immune responses and systemic toxicity, and heart tissue will be analyzed for cardiotoxicity associated with doxorubicin treatment. Lastly, human mammary epithelial and breast cancer cell lines will be treated with ginsenosides and/or cytokines to determine the signaling and apoptotic pathways that may be responsible for ginseng-induced sensitization to doxorubicin therapy. We hypothesize that the bioactive ginseng constituents will act in concert through different mechanisms of action to maximize the safety and complementary effectiveness of ginseng. These data will provide the first translational step towards providing evidence-based information to heath care professionals and the public regarding the use of ginseng and its constituent-enriched extracts in complementary breast cancer therapy. . PUBLIC HEALTH RELEVANCE: This R21 grant project will determine how ginseng's ginsenoside and ginseng polysaccharide constituents contribute to the complementary effectiveness of ginseng during doxorubicin treatment for breast cancer in a nude mouse model; and, secondly, address the mechanisms of action of ginseng's constituents. It is our hypothesis that these bioactive ginseng constituents act together through different mechanisms of action to maximize the safety and complementary effectiveness of ginseng. These data will provide the first translational step towards providing evidence-based information to heath care professionals and the public regarding the use of ginseng and its constituent-enriched extracts in complementary breast cancer therapy.