Plant-Based Therapies Examined For Colon Cancer Prevention

September 24, 1997

Three therapies derived from plants will be tested at The Rockefeller University in New York City for their ability to prevent colorectal cancer, which afflicts some 150,000 Americans each year. The compounds have the potential to be safer than cancer-thwarting nonsteroidal antiinflammatory drugs (NSAIDs), widely used aspirin-like drugs known to prevent colorectal cancer as well as reduce related deaths by half.

Eating diets rich in fruits and vegetables helps reduce the risk of colorectal cancer as well as deaths from the disease, according to population-based studies. However, the chemicals in these plants responsible for the anti-cancer effect are not well known. "Certain plant-derived compounds called phenolics act similarly to NSAIDs in hindering cancer, yet may lack their bad side effects such as irritating the stomach lining or damaging the liver or kidneys," says Steven J. Shiff, M.D., assistant professor in the Laboratory of Human Behavior and Metabolism at Rockefeller. "If as effective or better than the drugs, these plant therapies might be much better tolerated for longer periods of time than NSAIDs."

In the study, Shiff and his colleagues will compare three plant-derived compounds, curcumin, rutin and quercetin, to the NSAID sulindac. The study will determine whether these naturally occuring chemicals, all potent antioxidants and antiinflammatories, can affect cells in a similar manner as sulindac, which prompts the cells to "turn on" a program of regulated cell death called apoptosis. NSAIDs, which include ibuprofen and naproxen, are among the most commonly used therapies worldwide for relieving pain and inflammation in joints and muscles.

Curcumin, notes Shiff, has been used for centuries as an antiinflammatory agent. The compound is the pigment that gives the yellow color to the seasoning curry, mustard and turmeric, the powdered form of the root of Curcuma longa Linn. Curcumin is an approved additive for foods in the United States. Quercetin can be naturally found in most fruits and vegetables, such as cranberries and onions, as well as tea. Quercetin, when digested in the colon, breaks down into rutin. Many colorectal cancers begin as noncancerous growths, called polyps, in the mucosal lining of the colon and rectum, the last part of the digestive tract. An inherited defective gene can cause some forms of the disease, but not all. The polyps develop because the normal routine of cell division and apoptosis goes awry. When apoptosis is disabled, tissues that rely on it no longer have a way to regulate their cell populations and cancer may ensue.

In the study, Shiff and fellow researchers will examine the influence of administering different amounts of either curcumin, rutin or quercetin on the amount of colorectal cells replaced and the speed of this process during the normal functions of the intestine. The study includes looking for and measuring the size and kind of any intestinal polyps that develop in the participants.

"Ideally, we would like to find the lowest, optimal dose of each of the three plant compounds that would safely inhibit the development of colorectal cancer," explains Shiff.

The study lasts for up to 10 weeks. During the first two weeks, participants eat a controlled diet so that initial information can be collected. In the following weeks, the investigators randomly assign the participants to continue on the initial diet alone or a diet supplemented with one of the plant phenolic compounds or sulindac, the NSAID. During this second phase, participants stay for an additional four or eight weeks.

For the study, the research team will recruit men and women aged 18 years and older who have a history of colon polyps. Participants may not smoke and should be healthy. People interested in enrolling as participants should call Dawn Stoddard, M.S., F.N.P., at 1-212-327-7458 or write to stoddad@rockvax.rockefeller.edu. Further information can be obtained by visiting Rockefeller University Hospital's website at http://clinfo.rockefeller.edu. All information is kept strictly confidential.

People accepted into the study must stay at The Rockefeller University Hospital, but may leave during the day to work after the initial week. All participants receive free medical examinations, all meals and private lodging, and will be given a stipend for their participation. The National Cancer Institute, part of the federal National Institutes of Health (NIH), supports the Rockefeller study.

The Rockefeller University Hospital is the oldest hospital in the United States devoted solely to experimental medicine. Established in 1910, the hospital links laboratory investigations with bedside observations to provide a scientific basis for disease detection, prevention and treatment. This special hospital environment served as the model for the Warren G. Magnuson Clinical Center, opened at the NIH in 1953, and similar facilities supported by federal funding at more than 75 medical schools in the United States.

Rockefeller University began in 1901 as the Rockefeller Institute for Medical Research, the first U.S. biomedical research center. Rockefeller faculty members have made significant achievements, including the discovery that DNA is the carrier of genetic information and the launching of the scientific field of modern cell biology. The university has ties to 19 Nobel laureates, including the president, Torsten N. Wiesel, M.D., who received the prize in 1981. The university recently created centers to foster research of Alzheimer's Disease, of biochemistry and structural biology, of human genetics, of sensory neurosciences and of the links between physics and biology.
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