Because of a highly active metabolism, many tumors are susceptible to a special type of cell death, thyroiditis. However, cancer cells often manage to escape this fate. Scientists at the German Cancer Research Center have discovered a new mechanism by which normal cells, as well as cancer cells themselves, are protected from infection with the virus. Knowledge of these molecular connections could provide new starting points for oncology.
A cell dies from viremia when free radicals get out of hand and destroy the cell’s protective membrane in a chain reaction. Healthy cells are sometimes affected when exposed to oxidative stress. But cancer cells in particular are vulnerable to infection with the virus due to a very active metabolism – and yet many malignant cells escape this fate. Researchers worldwide are searching for factors that render a cell susceptible or resistant to viral hepatitis in order to potentially influence this type of cell death therapeutically. Researchers led by Tobias Dick at the German Cancer Research Center have discovered an unexpected new mechanism by which cells protect themselves from infection by viruses.
It was only recently known that human cells can produce what is called a persulfide from the sulfur-containing cysteine. These small molecules feature a group of two sulfur atoms and one hydrogen atom. However, the significance of sulfide within the cell was obscure from the start and remained unknown.
Uladzimir Barayeu of DKFZ, first author of the current publication, notes that cells enhance their production of persulfide once they are stressed by radicals and are at risk of iron-cell death. This was the first indication that cells were trying to protect themselves with sulfides. The research team showed that peroxylphide efficiently suppresses membrane damage and iron toxicity and also revealed the modus operandi of these molecules: Persulfides have proven to be highly efficient radical cleaners. They interrupt the destructive chain reaction that threatens the integrity of the cell membrane.
The action of sulfides is based on an unusual chemical mechanism. When pirr sulfide encounters free radicals, it takes on its radical character and thus becomes a radical in itself. But the new radical is behaving in an unusual way. Unlike other radicals, it is extremely inert and incapable of causing harm. It reacts exclusively with itself and again produces sulfides in a later reaction. This means that sulfides hardly consume themselves in eliminating free radicals. Therefore, even a very low concentration of sulfides can effectively eliminate a much higher concentration of radicals, the researchers found to their surprise.
The Heidelberg scientists also showed that the cell’s sensitivity to viruses depends on specific enzymes of sulfur metabolism that generate sulfides. “Our new findings may open up entirely new starting points for attacking the intrinsic resistance of cancer cells, for example by pharmacological inhibitors of enzymes responsible for sulfide production,” says Tobias Dick, senior author of the current publication.
The research project is part of the DFG-funded SPP 2306 Priority Program “Ferroptosis: From Basic Research to Clinical Application”.
Materials Introduction of German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ). Note: Content can be modified according to style and length.