Plant-Based Therapies Examined For Colon Cancer Prevention

Eating diets rich in fruits and vegetables helpsreduce the risk of colorectal cancer as well as deathsfrom the disease, according to population-basedstudies.  However, the chemicals in these plantsresponsible for the anti-cancer effect are not wellknown.  "Certain plant-derived compounds calledphenolics act similarly to NSAIDs in hindering cancer,yet may lack their bad side effects such as irritatingthe stomach lining or damaging the liver or kidneys,"says Steven J. Shiff, M.D., assistant professor in theLaboratory of Human Behavior and Metabolism atRockefeller.  "If as effective or better than thedrugs, these plant therapies might be much bettertolerated for longer periods of time than NSAIDs."

In the study, Shiff and his colleagues will comparethree plant-derived compounds, curcumin, rutin andquercetin, to the NSAID sulindac.  The study willdetermine whether these naturally occuring chemicals,all potent antioxidants and antiinflammatories, canaffect cells in a similar manner as sulindac, whichprompts the cells to "turn on" a program of regulatedcell death called apoptosis.  NSAIDs, which includeibuprofen and naproxen, are among the most commonlyused therapies worldwide for relieving pain andinflammation in joints and muscles.

Curcumin, notes Shiff, has been used for centuries asan antiinflammatory agent.  The compound is thepigment that gives the yellow color to the seasoningcurry, mustard and turmeric, the powdered form of theroot of Curcuma longa Linn.  Curcumin is an approvedadditive for foods in the United States. Quercetin canbe naturally found in most fruits and vegetables, suchas 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 andrectum, the last part of the digestive tract.  Aninherited defective gene can cause some forms of thedisease, but not all.  The polyps develop because thenormal routine of cell division and apoptosis goesawry.  When apoptosis is disabled, tissues that relyon it no longer have a way to regulate their cellpopulations and cancer may ensue.

In the study, Shiff and fellow researchers willexamine the influence of administering differentamounts of either curcumin, rutin or quercetin on theamount of colorectal cells replaced and the speed ofthis process during the normal functions of theintestine.  The study includes looking for andmeasuring the size and kind of any intestinal polypsthat develop in the participants.

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

The study lasts for up to 10 weeks.  During the firsttwo weeks, participants eat a controlled diet so thatinitial information can be collected.  In thefollowing weeks, the investigators randomly assign theparticipants to continue on the initial diet alone ora diet supplemented with one of the plant phenoliccompounds or sulindac, the NSAID.  During this secondphase, participants stay for an additional four oreight weeks.

For the study, the research team will recruit men andwomen aged 18 years and older who have a history ofcolon polyps.  Participants may not smoke and shouldbe healthy.  People interested in enrolling asparticipants should call Dawn Stoddard, M.S.,F.N.P., at 1-212-327-7458 or write tostoddad@rockvax.rockefeller.edu.  Furtherinformation can be obtained by visiting RockefellerUniversity Hospital¹s website athttp://clinfo.rockefeller.edu.  All information iskept strictly confidential.

People accepted into the study must stay at TheRockefeller University Hospital, but may leave duringthe day to work after the initial week.  Allparticipants receive free medical examinations, allmeals and private lodging, and will be given a stipendfor their participation.  The National CancerInstitute, part of the federal National Institutes ofHealth (NIH), supports the Rockefeller study.

The Rockefeller University Hospital is the oldesthospital in the United States devoted solely toexperimental medicine.  Established in 1910, thehospital links laboratory investigations with bedsideobservations to provide a scientific basis for diseasedetection, prevention and treatment.  This specialhospital environment served as the model for theWarren G. Magnuson Clinical Center, opened at the NIHin 1953, and similar facilities supported by federalfunding at more than 75 medical schools in the UnitedStates.

Rockefeller University began in 1901 as theRockefeller Institute for Medical Research, the firstU.S. biomedical research center. Rockefeller facultymembers have made significant achievements, includingthe discovery that DNA is the carrier of geneticinformation and the launching of the scientific fieldof modern cell biology.  The university has ties to 19Nobel laureates, including the president, Torsten N.Wiesel, M.D., who received the prize in 1981.  Theuniversity recently created centers to foster researchof Alzheimer's Disease, of biochemistry and structuralbiology, of human genetics, of sensory neurosciencesand of the links between physics and biology.