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Cultivating Arid Land Crop Plants with Anticancer Activity
By moniquegarcia on Thu, 08/29/2013 - 11:28am
Plants of the family Solanaceae are used as food and in traditional medicines all over the world. The powdered roots and/or extracts derived from roots of the winter cherry plant—Withania somnifera (L.) Dunal (family: Solanaceae)— have been used for more than 3,000 years in India as a general tonic to build stamina, improve mental concentration, relieve stress and enhance health. Commonly known as “ashwagandha” or Indian ginseng in Ayurvedic medicine, scientific tests on the preparation have shown that it has anti-inflammatory, cardio-protective, antioxidant and antitumor properties, among others. Withania is widely cultivated for commercial use in its native India, and also in the Middle East and in North America. Ashwagandha is sold as a dietary supplement in the United States and Europe. The compound withaferin A, scientifically studied since the 1960s, seems to play the largest role in the plant’s anticancer effects by reducing tumor mass and preventing the growth of blood vessels that make a tumor malignant. It also shows promise in treating Alzheimer’s and Parkinson’s diseases.
Description of Action:
University of Arizona scientists at the Southwest Center for Natural Products Research and Commercialization (or Natural Products Center, NPC), in collaboration with the Whitehead Institute at the Massachusetts Institute of Technology, have recently shown that withaferin A is effective in reducing brain tumor mass in animals at non-toxic doses. The NPC team used an entirely nontraditional method—aeroponics—to produce bulk amounts of withaferin A needed for biological evaluation. In aeroponics, plants are set over enclosed chambers where their suspended roots are misted with water and nutrients, instead of growing in soil. The UA College of Agriculture and Life Sciences provided funding for the project.
Similarly, in a collaborative project with Nuvogen Research, a small Tucson-based company, a lead compound isolated from the NPC’s library of extracts from Sonoran Desert plants has shown activity against prostate cancer. This lead compound derived from an arid land plant has been structurally modified to improve its stability. Invention Disclosures have been filed for this discovery and the activity of the synthetically modified compound. This compound is currently being tested in animal models. The arid land plant containing this compound is rare and difficult to cultivate, however NPC scientists have been able to grow this plant in the greenhouse using the same innovative aeroponic technology as described for winter cherry. They are obtaining the promising compound in large quantities, toward the goal of yielding enough of the synthetically modified compound required for preclinical evaluation.
These are just two examples of hundreds of such compounds the NPC has isolated, characterized and evaluated since its inception in 1996. The center searches for compounds in desert plants and their associated microorganisms that can improve human health and also be developed as potential industrial products in Arizona. The work focuses on economical methods for producing value-added natural products from plants and associated microorganisms; natural products make up 60 percent of the anticancer agents that are commercially available or are in late stage clinical development.
Using the aeroponic system for cultivation yielded Withania plants with about five times the biomass produced in soil-grown plants. The nontraditional method has produced more than 30 grams of the active compound withaferin A in several greenhouse operations at NPC. Withaferin A normally costs about $300 for just 5 milligrams, thus the potential value of the test crop was about $1,800,000. So far, the NPC has provided over 20 g of Withaferin A to collaborators at Whitehead Institute, MIT and Dartmouth College of Medicine. And although Withania usually takes two to three years to mature to be commercially viable, it took just six to nine months in this study. The patent for the production of withaferin A by the aeroponic technique was filed in 2011 by UA and MIT.
The work on the compound active against prostate cancer focuses on late stage Hormone Refractory Disease (HRD), for which no effective therapies currently exist. This stage kills more than 20,000 men per year in the United States alone. In addition to the potential for saving and/or prolonging thousands of lives, the direct target, a substance called PCa (prostate cancer a), represents a large market—greater than $3 billion—that remains focused on hormone ablation therapy. Many companies are active in this area and will be potential partners for commercial development.