Virtually at random, researchers plucked a native plant called Mundulea sericea out of the rich foliage of the remote jungles of Zimbabwe a few years ago, packed it up and shipped it to Chicago, to become what is today seen as a promising compound to prevent skin, breast and lung cancers.
The rare plant is one of more than 2,000 collected worldwide, from Puerto Rican rain forests to Hong Kong villages, in the past six years by a University of Illinois at Chicago program in search of cancer-preventing plants.
Researchers routinely comb the jungles for exotic plants that may help in chemotherapy, or the treatment of cancer. But the UIC team is unique because it seeks plants that are chemopreventive, or prevent cancer, and it has a one-of-a-kind testing system to detect the one out of every 100 plant compounds worth pursuing.
The program is at the fore of the developing field of cancer prevention, which has only in recent years gained prominence with the formation of an international medical society on the subject and the medical breakthrough of the breast cancer prevention drug tamoxifen.
“It’s proven–we can prevent cancer,” said Vernon Steele, program director of cancer prevention at the National Cancer Institute. “It used to be a theory. We need more funding to expand the field. The majority of money is spent on therapy.”
Within the field, UIC’s program has gained credence as it has continued to discover compounds that have made it into the cancer institute pipeline for human testing; the institute is currently conducting animal testing of three promising UIC compounds. Earlier this summer, the institute gave the program $6.2 million to continue its work. The recent federal suspension of virtually all human research at UIC does not affect the chemoprevention program because it only involves animal testing.
So far, the most advanced and high-profile discovery of the program is an inedible legume from Peru that yielded resveratrol, which tests have shown helps prevent skin, breast and colon cancers.
The program’s leader, John Pezzuto, a professor and associate dean for research and graduate education in the College of Pharmacy, made headlines in 1997 when he realized that resveratrol was also found in a far more common source: red wine. This month, UIC was given federal approval to conduct more advanced testing on resveratrol, in preparation for human trials.
“We are moving toward a pill, a one-a-day that people could take to help them prevent cancer. Or, it could be genetically engineering food to help prevent cancer in the general population,” said Pezzuto, a biochemist.
Of the world’s 250,000 flowering terrestrial plants, the team collects about 200 a year from more than 30 countries based on whim, the novelty of a plant, and advice from local experts and native residents, who may have medicinal uses for the plants. While it may seem like a lot of plants to pick in search of a single promising agent, the program’s approach works, Pezzuto says.
“We are discovering new compounds . . . and finding known compounds that have activity that no one has ever known of before,” Pezzuto said.
UIC researchers take expeditions to collect the plants themselves, as well as working with colleagues worldwide to obtain the material. Currently, the team is most excited about a handful of cancer-preventing compounds that are derived from plants as exotic as the Zimbabwe plant to basic grocery-store broccoli.
Many drugs in use today are obtained from plants. Medicine for congestive heart failure is derived from foxglove; the active ingredient in drugs for gastric ulcers comes from the flowering plant nightshade; snake root has given us medication to prevent high blood pressure; and the poppy produced the painkiller codeine.
“Natural products are a primary source of new agents to prevent cancer,” said Steele.
And he said Pezzuto “has one of the best set-ups in this country; they are trying to develop set-ups like this in other countries. With his collection of plants . . . and extracting and testing, that’s a fairly unique and comprehensive program he has.”
Along the way, prevention studies have been building a solid reputation.
“Twenty-five or 30 years ago, chemoprevention was seen as a bit off the wall. There’s general acceptance now that this is a legitimate way to deal with this,” said Michael Sporn, professor of pharmacology at Dartmouth Medical School and former chief of the laboratory of chemoprevention at the cancer institute.
“I’m a strong believer that the ultimate way we’re going to deal with the cancer problem is finding ways to prevent this disease rather than waiting until you get it and then trying to cure it,” said Sporn, who is on an advisory committee overseeing the UIC program.
Plant shipments come regularly to UIC’s field station, a serviceable network of greenhouses and storage areas in Downers Grove that is filled with the smell of herbs and mold. Lying about are boxes and crates of seeds, fruit, bark, branches, needles, leaves and stems. The material is dried in flat, wooden bins under natural light or in small ovens, then pulverized by a grinder.
The process for determining whether a plant could prevent cancer starts with a series of cellular tests. Out of 100 plant extracts, three may emerge from a series of tests using cancerous cells and other reactions to gauge the cancer-preventing qualities of an extract.
For example, in one test, skin cells are treated with a substance known to promote tumors, which should cause a certain enzyme level to rise. But if the plant extract suppresses the enzyme level, that action is consistent with blocking a cancer, Pezzuto said.
The three most promising compounds are then tested in a more complicated model that measures its effectiveness in preventing the formation of a tumor in a mouse mammary gland. It is then run repeatedly through the various cellular tests to eliminate the portions of the compound that are not active. Eventually, a single active chemical in a compound emerges. Researchers can then determine its chemical structure, whether it is already known, how it works and if it can be synthesized.
Of every 100 plants tested, only one contains a compound worth further testing.
After more laboratory testing to understand how the compound works, animal testing begins. A 120-day animal test is conducted on the most successful cancer-preventing compounds, which are given to animals at the same time as cancer-causing chemicals to assess whether the compound thwarts the development of cancer.
Harry Fong, a professor in the College of Pharmacy and co-investigator of collecting plants, says that searching native areas for plants that have traditional health uses is a natural.
“In Western medicine, we look for short-term curative powers, but in traditional medicine, they take a holistic approach and many traditional medicines are preventive,” Fong said. “Most people in these areas are willing to talk, to share their knowledge.”
