Impact Summary
Scientists at the University of Arizona's Southwest Center for Natural Products Research and Commercialization (SCNPRC) have discovered several compounds in desert plants that can significantly inhibit the growth of tumors and that are associated with Traditional Chinese Medicine and Indian Ayurvedic Medicine. The protein target of one of these compounds was determined and validated as a new target for anticancer drug discovery. They have also found a natural compound occurring in a plant-associated microorganism that has been shown to make the model plant, Arabidopsis thaliana, able to withstand high temperatures up to 45 degrees Celsius, or 113 degrees Fahrenheit, with significant implications for desert agriculture.
Issue
Scientists at the Office of Arid Lands Studies’ Southwestern Center for Natural Products Research and Commercialization (SCNPRC) are working with universities in and outside the United States, with agrochemical and pharmaceutical companies, and with other commercial entities to develop new biological and industrial products. The SCNPRC is part of the University of Arizona College of Agriculture and Life Sciences. The goals are to discover 1) specialty chemicals in indigenous desert plants that can be grown as industrial cash crops; 2) plant-associated microorganisms that can be used to produce pharmaceuticals and natural products with agricultural implications and 3) manipulation of biosynthetic genes of microorganisms capable of producing biologically active natural products. Natural product-based anti-cancer and anti-infective drugs and agrochemicals are in particular demand.
What has been done?
The SCNPRC team selects plants and plant-associated microorganisms in collaboration with other scientists and evaluates them for useful biological activities. If active, the scientists separate and characterize the natural compounds responsible for the activity, and determine how to cultivate and process these organisms on a commercial scale. In the case of anti-cancer agents, those showing promise will proceed into further testing for efficacy and toxicity. Scientists are currently pursuing several plant and microorganism-derived compounds for their in vitro and in vivo anticancer activity and also for their utility in improving agricultural production in arid lands. The drug discovery program includes anti-infective agents, especially those useful to treat HIV infections, and a program to study and manipulate microbial biosynthetic genes.
The SCNPRC group is collaborating with the UA Division of Plant Pathology, the Departments of Biochemistry and Biophysics, Immunology, Pediatric Oncology and Surgery, the Arizona Cancer Center, Arizona State University, Translational Genomics Institute, Josephine Ford Cancer Center, Harvard University, Whitehead Institute, China Pharmaceutical University, South Carolina Oncology Institute and DuPont Crop Protection Division.
Impact
A natural compound occurring in a plant-associated microorganism has been shown to make the model plant, Arabidopsis thaliana, thermotolerant-able to withstand high temperatures up to 45 degrees Celsius, or 113 degrees Fahrenheit. It has anticancer activity, one of the most-cited paper A patent application for this unusual activity of a natural product has been filed. Further work pursued in collaboration with Harvard University and the Whitehead Institute has shown that growing of Arabidopsis together with the fungus producing this compound also confers thermotolerance. Implications of these findings in arid land agriculture are currently being studied in collaboration with DuPont Crop Protection. If successful in creating drought and cold tolerant crop plants with this new approach, it will possibly serve as an alternative to genetic manipulation.
Animal studies of anti-cancer compounds isolated from two medicinal plants, one used in Traditional Chinese Medicine and the other in Indian Ayurvedic Medicine, have shown encouraging anti-angiogenic activity-the ability to halt cancerous growths by inhibiting the spread of blood vessels that nourish tumors and enable them to spread into vital organs of the body. The two compounds are also capable of 100 percent inhibition of cancer proliferation in vitro at low concentrations. A patent application has been filed for the discovery of a novel anti-cancer drug target. This is part of an ongoing effort to find natural products with unique applications from arid lands organisms, allowing conservation and maintenance of the delicate desert ecosystem.
Funding
- Arizona Agricultural Experiment Station-Natural Products Center
- Arizona Biomedical Research Commission
- Prostate Cancer Foundation (CaP CURE)
- public health funding from NIH and NCI
- Department of Defense Prostate Cancer Program
- American Institute for Cancer Research
Contact
Leslie GunatilakaSW Center for Natural Products
Research and Commercialization
The University of Arizona
250 E. Valencia Road
Tucson, AZ 85706
Tel.: (520) 741-1691
FAX: (520) 741-1468
Email: leslieg@ag.arizona.edu