Novel Breast Cancer Anti-Angiogenic Compounds
|Institution:||University of California, Los Angeles|
Mai Brooks , M.D., FACS -
|Award Cycle:||1999 (Cycle V)||Grant #: 5IB-0039||Award: $67,611|
|Innovative Treatments>New drug design: creative science|
Initial Award Abstract (1999)
Two decades of experimental evidence has demonstrated that the growth and metastasis of breast cancer are dependent on angiogenesis, the development of new blood vessels. Although over 30 anti-angiogenesis compounds are in clinical trials, we are focusing our search on natural compounds that could readily be given as safe, oral inhibitors. Our search has revealed that an extract from the plant Livistona, a palm tree, can inhibit experimental angiogenesis and suppress breast tumor growth in animal model systems. Preliminary analysis showed that the active compounds are stable to heat, acid, and most likely are small organic molecules. So far, there has been no observed toxicity in mouse experiments. In this study, we propose to further isolate and identify the exact chemical structure of the active anti-angiogenesis compound(s). This purification/chemical analysis will be accomplished by ion exchange chromatography, gas chromatography coupled with mass spectrometric analyses, nuclear magnetic resonance, infra-red spectroscopy, and X-ray crystallography. The resulting purified compound(s) will be tested for anti-angiogenesis activity in cellular assays and in mouse tumor models. The current list of drugs in development for treating angiogenesis looks promising. However, plant-based compounds have the potential advantage of use in more preventive (chronic) settings and in an orally active form. We think that the discovery of a potent anti-angiogenic drug with low toxicity would potentially be very useful in the treatment and prevention of breast cancer, especially in high-risk women or survivors at risk for recurrence.
Final Report (2001)
Note: This grant was extended one year to complete the scientific aims The growth and metastasis of solid tumors in general, and breast cancer in particular, are dependent on their ability to initiate and sustain new capillary growth, i.e. angiogenesis. With the goal of finding a potent anti-angiogenic drug that can be given orally, we have initiated a screening program in our laboratory designed to test a wide variety of plant extracts for anti-angiogenic activity. Our search has revealed that an extract from the plant Livistona can inhibit angiogenesis and suppress breast tumor growth in animals. There were no observed toxicities in mouse experiments. Thus far, we have carried out experiments in order to characterize and identify the chemical structure of the active compound(s). We have shown that the anti-angiogenic activity resides mostly in the shell of the plant seeds. Multiple chemical experiments have demonstrated that the anti-angiogenic compound(s) are best extracted by chloroform. Currently, we are conducting further studies using other methods of chemical analysis, as well as other functional assays. We think that the discovery of a potent anti-angiogenic drug with low toxicity would potentially be very useful in the treatment and prevention of breast cancer, particularly in elderly women who are not candidates for chemotherapy.
Livistona extract inhibits angiogenesis and cancer growth.
Index Medicus: Oncol Rep
Authors: Sartippour MR, Liu C, Shao ZM, Go VL, Heber D, Nguyen M
|Yr: 2001||Vol: 8||Nbr: 6||Abs:||Pg:1355-7|