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Research Newsletter-Spring/Summer 2007

LPI 10th ANNIVERSARY COLLOQUIUM

Genetic and epigenetic approaches to cancer prevention and therapy by dietary agents

Rod Dashwood, Ph.D.
Principal Investigator, Linus Pauling Institute;
Professor of Environmental and Molecular Toxicology, Oregon State University

Our research examines protective compounds found in foods that might prevent or lower the incidence of colorectal cancer.

Cooking meat at high temperatures can produce heterocyclic amine mutagens. The U.S. National Toxicology Program recently classified these compounds as "reasonably likely to be human carcinogens." They cause DNA damage and, in some cells, this leads to overproduction of a protein called betacatenin, resulting in colon cancer. A compound found in tea has been shown to reduce levels of beta-catenin in human colon cancer cells in vitro (experiments performed in cultured cells). This compound is present in all forms of tea (white, green, oolong, and black), but the highest concentrations are found in white and green teas. The compound in question, epigallocatechin- 3-gallate (EGCG), typically is not found in herbal teas. Our animal studies show that white tea given in place of the drinking water resulted in fewer pre-cancerous lesions induced by cooked-meat mutagens in the rat colon and lowered spontaneous intestinal polyps in mice.

Another pathway leading to colon cancer development involves the deactivation of tumor suppressor genes. As their name suggests, tumor suppressor genes prevent cells from developing into tumors and potentially leading to cancer. These tumor suppressor genes can be deactivated in cancer cells by an enzyme called histone deacetylase (HDAC).

We wanted to know if food compounds can act as HDAC inhibitors, thereby turning on these silenced tumor suppressor genes. One food compound called sulforaphane, which is found in cruciferous vegetables, was an effective HDAC inhibitor blocking the growth of human colon and prostate cancer cells in cell culture. Sulforaphane also decreased HDAC activity in various mouse tissues after feeding in the diet and inhibited HDAC activity in circulating blood cells of humans after they consumed sulforaphane-rich broccoli sprouts. There were fewer intestinal polyps in mice given sulforaphane or EGCG alone, compared to control animals, but sulforaphane and EGCG in combination did not appear to act synergistically in preventing tumor formation in mice.

Last updated May 2007