Researchers identify first genomic blueprint of cancer preventive compound found in broccoli
Discovery could lead to the identification of other cancer-preventing compounds
Using gene chip technology, researchers at the Johns Hopkins Bloomberg School of Public Health have identified the blueprint of genes and enzymes in the body that enable sulforaphane, a compound found in broccoli and other vegetables, to prevent cancer and remove toxins from cells. The discovery was made using a "gene chip" that allows researchers to monitor the complex interactions of thousands of proteins on a whole genome rather than one at time. The study is published in the September 15, 2002 issue of the journal Cancer Research, and is the first gene profiling analysis of a cancer-preventing agent using this approach. The researchers believe the findings provide a better understanding of the body's defense mechanisms and could lead to the identification of other cancer-preventing food compounds and strategies.
For the study, the researchers analyzed the downstream genomic targets of the transcription factor Nrf2 (Nuclear factor E2 p45-related factor 2), which scientists previously knew was activated in response to anticancer agents such as sulforaphane. The transcription factor, Nrf2, in response to cancer preventive agents, turns on genes and pathways inside the cell, whose products help in ridding the body of carcinogens.
"Carcinogens mutate the DNA in genes, which leads to cancer. Now, we know that sulforaphane present in broccoli can turn an extensive network of genes and pathways, which can annihilate a broad spectrum of carcinogens," said Shyam Biswal, PhD, assistant professor of environmental health sciences at the Johns Hopkins Bloomberg School of Public Health.
"With this study we've identified the specific genes regulated in response to a promising chemopreventive agent, which tells us how the process of cancer chemoprevention is occurring and provides us with a novel strategy for evaluating potential cancer preventive agents in future," explained Dr. Biswal.
Dr. Biswal and his colleagues studied the gene profile of small intestines of mice to identify the genes regulated by Nrf2. The researchers treated groups of mice with sulforaphane and compared the effects to control groups in which the Nrf2 gene was knocked off. "In summary, this study expands the scope of the positive, coordinated regulation of a wide variety of cellular defense proteins by Nrf2 and underscores the potential of Nrf2 activation as a strategy for achieving cancer chemoprevention," said Dr. Biswal.
"Identification of Nrf2-regulated Genes Induced by the Chemopreventive Agent Sulforaphane by Oligonucleotide Microarray" was written by Rajesh K. Thimmulappa, Kim H. Mai, Sorachai Srisuma, Thomas W. Kensler, Masayuki Yamamoto, and Shyam Biswal. It is published in the September 15, 2002 edition of "Cancer Research."
The study was supported by grants from the Maryland Cigarette Restitution Fund and the American Cancer Society.