Botanical-derived drug discovery for cancer therapy

描述（由申请人提供）：在筛选天然存在的血管生成抑制剂时，我们已经鉴定了来自植物蒲葵的提取物，其具有有效的抗血管生成和抗肿瘤活性，并且在小鼠中无毒。据我们所知，我们的是第一个出版物在英文文献中的这种提取物从蒲葵。我们假设蒲葵提取物抑制肿瘤发生和血管生成，蒲葵中的许多一种或多种活性成分所产生的作用可能对该提取物的化学预防或化学治疗应用至关重要。在这项创新的研究提案中，我们将根据体外抗增殖和抗血管生成试验确定提取物中的活性成分;研究这些成分在体内试验中使用时是否有效。我们第一阶段的具体目标如下：目标1：利用各种化学和分析技术，包括提取、色谱分离、核磁共振、光电二极管阵列、红外和高分辨率质谱，从蒲葵中分离和鉴定活性成分。目的2：研究甘草活性成分对体外乳腺致瘤性和抗原性的影响。将在乳腺肿瘤异种移植模型中检测活性组分。此外，我们将开始研究活性化合物的作用机制。考虑到在我们的动物模型中从植物提取物中观察到的低毒性，口服可用性，稳定性和有效的药理学活性，我们认为这项研究在努力开发针对乳腺癌和其他实体瘤的新型有效疗法方面具有特别高的价值。

DESCRIPTION (provided by applicant): In a screen for naturally occurring angiogenic inhibitors, we have identified an extract from the plant Livistona chinensis, which has potent anti-angiogenic and anti-tumor activity and is non-toxic in mice. To our knowledge, ours is the first publication in the English literature on this extract from Livistona chinensis. We hypothesize that the Livistona extract inhibits tumorigenesis and angiogenesis, and that the effects exerted by many one or more active components in Livistona chinensis may be critical to the chemopreventive or chemotherapeutic application of this extract. In this innovative research proposal, we will identify the active ingredient(s) in the extract based on the in vitro anti-proliferative and antiangiogenic assays; investigate whether these components have an effect when used in in-vivo testing. Our specific aims for Phase 1 are as follows: Aim 1: To isolate and identify the active component(s) from the plant Livistona chinensis using a variety of chemical and analytical techniques, including extraction, chromatographic separation, nuclear magnetic resonance, photo diode array, infrared and high resolution mass spectrometry. Aim 2: To test the effect of cach active component on in vitro breast tumorigenicity and antiogenesis assays. The active components will be tested in breast tumor xenograft models. Furthermore, we will begin to investigate the mechanism(s) of action exerted by the active compound(s). Considering the observed low toxicity, oral availability, stability, and potent pharmacologic activity in our animal models from the plant extract, we see this research of particular high value in the efforts to develop novel effective therapies against breast cancer, and possibly other solid tumors as well.