Botanical-derived drug discovery for cancer therapy

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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.