“We took the challenge to decipher the network of molecular pathways...”

This paper reveals the transcriptional targets of Nrf2 (by monitoring global gene expression) which was fundamental to understanding regulatory pathways that detoxify carcinogens. Recent evidence, including our current paper, shows Nrf2 to be one of the most important transcription factors because it is responsible for the induction of several dozens of antioxidants and carcinogen-detoxifying enzymes.

This work helped in deciphering the complex network of pathways which can be turned on by activation of Nrf2. These pathways act in concert for detoxification of a broad spectrum of carcinogens. Furthermore, this study provides the genomic blueprint of a promising cancer chemopreventive agent, Sulforaphane. This anti-carcinogenic compound is naturally found in broccoli and its efficacy is currently being evaluated for preventing cancer. The current findings provide a better understanding of how activation of Nrf2 by Sulforaphane could be effective for chemoprevention of cancer and other oxidative stress related diseases.

I was intrigued that most toxicants at non-lethal doses induce a battery of genes, which encode proteins and antioxidant enzymes, and help cells survive. These genes have antioxidant response elements and cells have evolved this defensive system to protect themselves from endogenous and exogenous toxicants. Over the years, it became clear to me that Nrf2 is a master regulator for many antioxidant genes, but its repertoire of genomic targets was not clear. We took the challenge to decipher the network of molecular pathways, which are regulated in response to activation of Nrf2 and determine a cell's survival in response to toxic insult.

Now we know that Sulforaphane, present in broccoli, can activate a master control protein, Nrf2, in cells that turn on an extensive network of antioxidant genes and pathways. The Nrf2 regulated pathways have the potential to annihilate a broad spectrum of carcinogens. Future clinical trials based on activation of the Nrf2 pathway will determine the efficacy of this strategy for preventing cancer.