Novel approaches for colon cancer prevention by types of dietary fat, pterostilbene and other food components


Bandaru S. Reddy1, H. Newmark1, Nanjoo Suh, nsuh@rci.rutgers.edu1, Agnes M. Rimando, arimando@msa-oxford.ars.usda.gov2, and Chintalapally V. Rao3. (1) Rutgers, The State University of New Jersey, Susan Lehman Cullman Laboratory for Cancer Research, 164 Frelinghuysen Road, Piscataway, NJ 08854, (2) USDA, ARS, Natural Products Utilization Research Unit, P.O. Box 8048, University, MS 38677, (3) University of Oklahoma Health Sciences Center, University of Oklahoma Cancer Institute, Department of Medicine, Oklahoma City, OK
Populations that have a high intake of saturated fats and calories have a higher risk for colon cancer development. Dietary fish oil and olive oil reduce the risk. In support of these observations, several preclinical studies using animal models provided evidence that high dietary saturated fats such as those in Western diets promote colon carcinogenesis whereas diets high in fish oil or olive oil, or low calories had no such promoting effect. Epidemiological studies have provided initial leads for the identification of naturally occurring candidate chemopreventive agents from fruits, vegetables and grains which are principal sources of micronutrients and several minor constituents including isoflavonoids, ω-3 PUFA, triterpenoids, polyphenols, isothiocyanates and stilbenes. Pterostilbene, a naturally occurring stilbene found in blueberries, was tested for its preventive activity against colon carcinogenesis. Administration of pterostilbene (40 ppm) significantly suppressed azoxymethane-induced formation of colonic aberrant crypt foci and multiple clusters of aberrant crypts. A very low dose (250 ppm) of Celecoxib, a COX-2 inhibitor, administered in high ω-3 PUFA diet suppressed colon tumorigenesis more efficiently than when it is given in a high fat Western-style diet. An important strategy to reduce the risks associated with the use of pharmacological agents is to identify combinations of agents with different modes of action that are very effective at very low doses. This approach is very important when a promising chemopreventive agent demonstrates significant efficacy but may produce toxic effects at high doses. The use of low doses of pharmacological agents with different modes of action in combination with healthy lifestyles seems to be a promising approach that may evolve into a better chemopreventive strategy for future human clinical trials. (Supported by USPHS grant CA-37763 from the National Cancer Institute)