Insights into the Anticancer Action of Sulforaphane

The enzymes act as scavengers for cancer-causing molecules before they can damage DNA and promote cancer. The researchers have also identified the transcription factor activated by sulforaphane and the specific genes regulated by this activation. These findings were published in the September 15, 2002, issue of Cancer Research.

The investigators, from the Johns Hopkins Bloomberg School of Public Health (Baltimore, MD, USA), employed gene chip technology to determine which small intestine mouse genes were turned on by the Nrf2 (nuclear factor E2 p45-related factor 2) transcription factor after its activation by sulforaphane.

Comparative analysis of gene expression changes between different treatment groups of wild-type and nrf2-deficient mice facilitated identification of numerous genes regulated by Nrf2, including previously reported Nrf2-regulated genes such as NAD(P)H:quinone reductase (NQO1), glutathione S-transferase (GST), -glutamylcysteine synthetase (GCS), UDP-glucuronosyltransferases (UGT), epoxide hydrolase, as well as a number of new genes. Also identified were genes encoding for cellular NADPH regenerating enzymes (glucose 6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, and malic enzyme), various xenobiotic metabolizing enzymes, antioxidants (glutathione peroxidase, glutathione reductase, ferritin, and haptaglobin), and biosynthetic enzymes of the glutathione and glucuronidation conjugation pathways.

"With this study we have 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 the future,” explained Dr. Shyam Biswal, assistant professor of environmental health sciences at Johns Hopkins and the study's senior author. "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.”



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