Anti-Cancer Ginsenosides: Their Interactions and Mechanisms of Action

说明(申请人提供)：人参是人类广泛使用的一种草药，用于治疗体力不足、食欲不振、恶病质和阳萎。在亚洲医学中，人参是治疗癌症的草药中的常见成分。最近的科学证据表明，人参及其皂苷成分在体外能有效地抑制癌细胞的增殖，在体内能抑制肿瘤的生长。已鉴定出几种具有抗癌活性的人参皂苷，但人参及其提取物中含有20多种人参皂苷。由于人参皂苷似乎发挥了人参及其提取物的大部分生物活性，了解人参皂苷如何相互作用影响人参的抗癌效力是很重要的。在初步研究中，我们发现人参皂苷可以增强或拮抗人参皂苷的抗癌作用。因此，我们的假设是，某些人参皂苷通过特定的作用机制抑制人乳腺癌细胞的增殖，而其他人参皂苷根据细胞增殖、肿瘤生长以及乳腺癌细胞基因和蛋白表达的变化而拮抗或增强抗癌人参皂苷的活性。R21建议将解决以下目标：为了确定生物相关人参皂苷单独或联合对体外培养的人乳腺癌细胞增殖的影响，我们将检测广泛剂量范围的生物相关人参皂苷对细胞增殖的影响，鉴定那些具有抗癌活性的人参皂苷，并结合人参皂苷来确定人参皂苷是否存在相互作用。其次，我们将确定特定的人参皂苷单独和联合作用于MCF-7细胞的机制。实际上，我们将使用商业抗体微阵列来确定单个人参皂苷对蛋白质表达的影响，并确定与单个人参皂苷的影响相比，人参皂苷组合是否会改变蛋白质表达。最后，我们将确定特定的人参皂苷组合对裸鼠体内MCF-7肿瘤生长的影响。小鼠将被接种MCF-7细胞，用特定的人参皂苷组合治疗，并将监测肿瘤的生长。鉴定抗癌人参皂苷并确定其他人参皂苷如何影响其活性，将是建立反映人参产品抗癌效力的人参皂苷图谱的重要第一步。

DESCRIPTION (provided by applicant): Ginseng is an herb widely used by humans to treat lack of stamina, loss of appetite and cachexia, and impotence. In Asian medicine, ginseng is a common component in herbals used for cancer treatment. There is recent scientific evidence that ginseng and its ginsenoside components are effective in inhibiting cancer cell proliferation in vitro and tumor growth in vivo. Several ginsenosides have been identified that exert anti-cancer activity, yet over 20 ginsenosides exist within ginseng and its extracts. As ginsenosides appear to exert much of the biological activity of ginseng and its extracts, it is important to understand how ginsenosides may interact with each other to influence the anti-cancer potency of ginseng. In preliminary studies, we have found that ginsenosides may augment or antagonize the effects of the anti-cancer ginsenosides. Thus, it is our hypothesis that certain ginsenosides will inhibit human breast cancer cell proliferation via specific mechanisms of action and that other ginsenosides will antagonize or augment the activities of the anti-cancer ginsenosides based on changes in cell proliferation, tumor growth, and gene and protein expression in breast cancer cells. This R21 proposal will address the following aims: To determine the effects of biologically relevant ginsenosides, alone or in combination, on human breast cancer cell proliferation in vitro, we will examine the effects of a wide dose-range of biologically relevant ginsenosides on cell proliferation, identify those ginsenosides with anti-cancer activity, and combine ginsenosides to determine if ginsenoside interactions exist. Secondly, we will determine the mechanisms of action of specific ginsenosides, alone and in combination, on MCF-7 cells. In effect, we will determine the effects of individual ginsenosides on protein expression using a commercial antibody microarray and determine if ginsenoside combinations alter protein expression compared to effects of the individual ginsenosides. Lastly, we will determine the effects of specific ginsenoside combinations on MCF-7 tumor growth in nude mice in vivo. Mice will be inoculated with MCF-7 cells, treated with specific ginsenoside combinations, and tumor growth will be monitored. Identifying the anti-cancer ginsenosides and determining how the other ginsenosides influence their activity, will be an important first step in establishing a ginsenoside profile that will reflect the anti-cancer potency of ginseng products.