June 25, 1999 A team of University of Illinois at Chicago researchers has obtained a five-year, $6.21 million grant from the National Cancer Institute to continue testing plants from around the world for their ability to prevent cancer.
The team, led by John Pezzuto, associate dean for research and graduate education in UIC's College of Pharmacy, has tested 2,500 natural products for their ability to prevent cancer since 1991. The finding that resveratrol, a substance found in red wine, inhibited tumor initiation, promotion and progression in mice provided the researchers with one of their most promising leads. Based on this discovery, the National Cancer Institute has selected resveratrol for pre-clinical testing.
"Dr. Pezzuto is a world-recognized scientist doing important work," said Michael B. Sporn, professor of pharmacology at Dartmouth Medical School and a founder of the field of cancer chemoprevention. "He already has identified some drugs that are very interesting from a chemopreventive point of view and his work should be encouraged." Sporn is a member of the external advisory board that will review the UIC team's research.
Pezzuto and his team are focusing their current research on dietary materials. The researchers' most promising leads have come from plant substances that they later discovered also are found in foods. The tests leading to the resveratrol finding, for instance, originally were conducted with a compound extracted from a legume collected in Peru. After the compound showed promise in early tests, the researchers isolated and identified the active agent as resveratrol.
"We think that if we identify and test substances that already can be found in our diets, it is more likely they will be safe. When you are talking about prevention, as opposed to treatment, the safety index has to be very high. In addition, if it's in our diet, then it will be more accessible to the general population," said Pezzuto.
The UIC team will test another 1,000 plants, some of which already have been obtained from Indonesia, Thailand and Panama. The researchers, using new, sophisticated methodologies and technology, will also re-test the 2,500 plants previously analyzed under the program.
Pezzuto's UIC team includes researchers from the university's medicinal chemistry and pharmacognosy, chemistry, mathematics, statistics and computer science, and surgical oncology departments. A researcher from Monsanto Life Sciences also is working on the project. The external advisory board members include scientists David S. Alberts from the University of Arizona, Koji Nakanishi from Columbia University and Lee Wattenberg from the University of Minnesota, in addition to Sporn.
UIC has developed the most broad-based drug discovery program in chemoprevention in the world. The researchers have developed a novel approach to drug discovery that has resulted in an extraordinarily high number of leads.
They begin by collecting plant samples using a variety of sources including the university's own field station, an extensive network of international contacts and field cultivation. Next the researchers test the plant materials for activity and, based on the results of these tests, separate out the active agents. The active agents then are evaluated for their potential to inhibit tumor initiation, promotion and progression in a variety of laboratory tests. Agents showing promise for chemopreventive activity are tested in laboratory animals. After identifying promising leads, researchers synthesize, structurally modify or produce these materials and test them in the laboratory and in laboratory animals.
The researchers have discovered roughly 70 active compounds. The most promising compounds under investigation by the UIC team are brassinin (from cruciferous vegetables such as Chinese cabbage) and its analog cyclobrassinin; sulforaphane (from broccoli) and its analog sulforamate; withanoloids (from tomatillos); and the stilbene resveratrol (from red grapes and peanuts among other foods). Other important leads not derived from edible plants include the flavanoid bromoflavone and the rotenoid deguelin.
"The enormous potential of cancer chemoprevention is broadly recognized, but we have not yet reached the point where the general population can benefit," Pezzuto said. "We hope our work ultimately will yield clinically useful agents. Beyond this goal, our discoveries of chemopreventive agents should be useful in helping the scientific community understand the mechanisms by which they prevent cancer."
Researchers in UIC's College of Pharmacy are working on two other large-scale drug discovery projects. The Fogarty International Center, funded by the National Institutes of Health, National Science Foundation and Department of Agriculture, recently awarded a $2.4 million International Cooperative Biodiversity Groups grant to D. Doel Soejarto, professor of pharmacognosy. Soejarto and his team are collaborating with researchers, tribal groups and healers in Vietnam and Laos to discover the medicinal properties of native plants. The team is implementing a new approach to drug discovery that fosters conservation and economic development in developing countries.
The National Cancer Institute has renewed funding for a project, led by Douglas Kinghorn, professor of pharmacognosy, to discover drugs from plants that may effectively be used to treat cancer. This project is in its ninth year and has received $4.2 million in renewed funding.
With 25,000 students, the University of Illinois at Chicago is the largest and most diverse university in the Chicago area. UIC is home to the largest medical school in the United States and is one of the 88 leading research universities in the country. Located just west of Chicago's Loop, UIC is a vital part of the educational, technological and cultural fabric of the area.
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