Most cancer treatments attack rapidly dividing cells, but they often also harm healthy cells. This damage can cause serious side effects. Researchers are working to design treatments that more precisely attack cancer cells without damaging normal tissue.
An international research team led by the University of Geneva (UNIGE) and the University of Marburg has identified a potential new strategy. They found that a mirror version of cysteine, a sulfur-containing amino acid, could significantly slow the growth of certain tumors while having little effect on healthy cells. This compound is primarily absorbed by certain cancer cells and interferes with important biological functions such as cellular respiration and DNA production. In mice, this effect significantly slowed the progression of aggressive breast tumors. This research natural metabolism.
Understanding mirror image amino acids
Amino acids are small molecules that serve as building blocks of proteins. They connect like beads on a thread to form the proteins necessary for living things. Twenty amino acids are used to build proteins found in all living organisms.
Two versions of these molecules exist, known as L (levorotatory) and D (dextrorotatory). The two forms are mirror images of each other, similar to the difference between a human’s left and right hand. They have the same chemical composition but different three-dimensional structures. Human biology relies almost entirely on the L form to build proteins, while the D form is rarely used.
D-cysteine slows cancer cell growth
Researchers led by Jean-Claude Martinu, professor emeritus at UNIGE’s Department of Molecular and Cell Biology, investigated how different amino acids affect the growth of cancer cells. Their experiments revealed that the D version of cysteine (D-Cys), which contains a sulfur atom, can strongly inhibit the growth of certain cancer cells in laboratory experiments. However, healthy cells were not affected.
“This difference between cancer cells and healthy cells can be easily explained: D-Cys is taken up into cells via a specific transporter that is only present on the surface of certain cancer cells,” explains Josephine Zangari, a PhD student in Martinu’s lab and lead author of the study. “In fact, when we expressed this transporter on the surface of healthy cells, we observed that those cells stopped proliferating in the presence of D-Cys.”
How this molecule interferes with cancer cell metabolism
In collaboration with Professor Roland Rill and his team at the University of Marburg, the researchers revealed how D-Cys harms cancer cells.
“It blocks an essential enzyme called NFS1 in mitochondria, the cell’s ‘powerhouses’. This enzyme plays a key role in the production of iron-sulfur clusters, small structures essential for many processes such as cellular respiration, the production of DNA and RNA, and the maintenance of gene integrity,” explains Roland Rill.
When NFS1 is blocked, several important cellular functions become dysfunctional. Cancer cells have decreased respiration, increased DNA damage, and cell cycle arrest. These effects prevent cells from continuing to grow and divide.
Delaying tumor growth in mice
To test whether this approach would work in vivo, the scientists treated mice with aggressive mammary tumors that are usually difficult to treat. The results were promising. Tumor growth was significantly slowed and the animals showed no significant side effects.
“This is a very positive signal. We now know that we can use this specificity to target specific cancer cells,” says Jean-Claude Martinu. “However, we need to determine whether D-Cys can be administered to humans in effective doses without causing harm.”
If further research confirms its safety and efficacy in humans, D-cysteine could become a relatively simple and selective treatment for cancer, producing high levels of the transporter responsible for bringing this molecule into cells. This strategy may also help prevent metastasis, a key step in cancer progression.
