Hydrogen Peroxide: A Messenger Important in Cancer Cell Survival

P. Andrew Karplus, Ph.D.
Department of Biochemistry and Biophysics, Oregon State University
P30ES00210 (Joseph Beckman, Ph.D., Director)

Background: Hydrogen peroxide, known mostly as a common antiseptic, is also a product of aerobic metabolism. As an organism consumes oxygen, small amounts of hydrogen peroxide are formed as a by-product. All aerobic organisms have evolved systems to control this simple molecule so that it doesn't accumulate in quantities sufficient to kill or damage cells. One such mechanism is the enzyme peroxiredoxin. Peroxiredoxin and other enzymes, such as catalase, act to destroy hydrogen peroxide. The story might end there, but there is a growing body of evidence that hydrogen peroxide is important for cell signaling and communication. A team of researchers, using support from the NIEHS Center at Oregon State University, has discovered that differences in the bacterial and human forms of peroxiredoxin affect how well it functions. These findings suggest that the enzyme plays a role in cancer development.

Advance: The team showed that the human enzyme is over 100 times more sensitive to damage by hydrogen peroxide than is the bacterial enzyme, and they revealed the structural explanation of this difference. They postulated that this must have evolutionary value; that perhaps the human peroxiredoxin acts like a "floodgate" keeping resting levels in control, but allowing higher levels to signal the cell to undergo programmed cell death.

Implication: What started as a basic research investigation into the function of the enzyme turned out to have implications for cancer therapy. Some cancer drugs, such as cisplatin used in testicular cancer, cause an increase in the production of hydrogen peroxide killing the cells from the inside out. Cancer cells that are resistant to cisplatin or other cancer therapies such as radiation, seem to be making larger amounts of peroxiredoxin which degrades the hydrogen peroxide before it has a chance to kill the cell.

Citation: Wood ZA, Poole LB, Karplus PA. Peroxiredoxin evolution and the regulation of hydrogen peroxide signaling. Science. 2003 Apr 25;300(5619):650-3.