We have cloned two thioredoxin reductases and have shown that they are selenium-containing enzymes, and the selenium is essential for their biological activity. This is an intriguing observation because selenium currently is being widely investigated as an agent to prevent the development of cancer. Our laboratory is currently involved in studies to determine if thioredoxin reductase, through regulation of thioredoxin, could be involved in the cancer-preventing activity of selenium. Our recent work has expanded into the field of functional genomics, using DNA arrays to study the effects of cancer drugs and altered thioredoxin signaling on multiple gene expression in cancer cells. Apoptosis Signaling Apoptosis, a form of programmed cell death, is a mechanism whereby normal tissue growth is limited, and the body is protected from the development of cancer by the elimination of cells that have damaged DNA and that might develop into cancer cells.
Apoptosis is also the mechanism by which many cancer drugs ultimately kill cancer cells.
One of the major limitations to cancer therapy is that cancer cells have apparently become resistant to apoptotic death. Understanding the way apoptosis is regulated in cancer cells could provide important insights into how to prevent the development of cancer and how to better treat cancer. We have been studying inhibitors of PI3K and have modified phosphatidylinositols as inhibitors of Akt to restore normal apoptosis to cancer cells. We have shown that these compounds inhibit tumor formation in animals, and they are being developed for eventual clinical trials in patients. Selected Publications Gasdaska PY, Berggren MM, Berry MJ, Powis G. Cloning, sequencing and functional expression of a novel human thioredoxin reductase.