Scientists at Wake Forest University School of Medicine have discovered a new way to eliminate cancer cells by inhibiting their ability to get rid of harmful waste.
According to the “Medical
How the new medicine works
“We all produce hydrogen peroxide constantly, but cancer cells produce more of it,” said Dr. W. Todd Luther, a professor of biochemistry at Wake Forest University School of Medicine. “If we inhibit peroxiredoxin-3, the hydrogen peroxide levels rise even more and the cancer cells are killed.”
The new treatment acts as a cleanup team inside cancer cells, settling inside mitochondria and degrading hydrogen peroxide before it becomes toxic. Cancer cells activate PRX3 and other antioxidant defenses to deal with the stress of their altered metabolism. Most people think antioxidants protect, but it turns out cancer cells protect, too.
Natural compounds
The research team based their work on thiostrepton, a natural product with anti-cancer properties, and dismantled the molecule piece by piece until they found the smallest fragment that still served its purpose.
The team discovered a small part of the compound that is able to bind to a protein called PRX3 and turn it off. PRX3 normally helps cancer cells get rid of harmful molecules, and when it is turned off, these molecules, such as hydrogen peroxide, accumulate so much that the cancer cells cannot survive.
Rare types of cancer
Mesothelioma, a rare and aggressive cancer often diagnosed in its advanced stages, is an example of the limitations of current treatment options, with patients often facing negative long-term outcomes. The new treatment is already being tested to treat mesothelioma through direct injection into the lung, but its size limits its wider use. The smaller piece represents a new opportunity to deliver the treatment intravenously and reach cancers throughout the body.
The smaller piece, called WF-242, was able to kill cancer cells just as effectively as thiostrepton while avoiding many of the unwanted interactions seen with the parent molecule.
Using cellular studies, the team showed that WF-242 is able to kill ovarian, lung, brain, prostate, and blood cancer cells. Instead of reducing oxidative stress in tumors, this strategy deliberately increases it. Because cancer cells are already working near their limits in dealing with hydrogen peroxide, they are more susceptible to this approach than normal cells.
