An international team led by the University of Geneva (UNIGE) and the University of Marburg has discovered that D-cysteine, the “mirror” form of the amino acid cysteine, can selectively slow the growth of certain cancer cells while sparing healthy ones. This discovery, published in Nature Metabolism, offers a promising new avenue for targeted cancer therapy with fewer side effects.
A New Approach to Reduce Treatment Side Effects
Most existing anticancer treatments damage both cancerous and healthy cells, leading to severe side effects. To overcome this challenge, scientists are seeking therapies that act exclusively on tumor cells. The UNIGE-Marburg team discovered that specific cancer cells preferentially absorb D-cysteine, a sulfur-containing amino acid, which disrupts vital processes like respiration and DNA synthesis and thereby inhibits tumor growth.
Understanding D- and L-Forms of Amino Acids
Amino acids are the fundamental building blocks of proteins, existing in two forms: L (levorotatory) and D (dextrorotatory). These forms are mirror images of each other—chemically identical but spatially different, much like left and right hands. The human body predominantly uses L-forms to synthesize proteins, while D-forms are rarely utilized.
Dr. Jean-Claude Martinou, Honorary Professor at the UNIGE Faculty of Science, and his team investigated how different amino acids influence cancer cell growth. They discovered that D-cysteine (D-Cys), which contains a sulfur atom, significantly inhibits the proliferation of certain cancer cells in laboratory settings but has no detectable effect on healthy cells.
Targeting Cancer Cells Through a Unique Transport Mechanism
Medicalxpress reported that the study revealed how D-Cys enters cells determines its selective effect. Joséphine Zangari, a Ph.D. student and first author of the study, explained, “A specific transporter on the surface of certain cancer cells imports D-Cys. When we artificially expressed this transporter on healthy cells, they also stopped proliferating in the presence of D-Cys.”
This finding suggests that the presence of this transporter could serve as a biological marker for identifying tumors that may respond to D-cysteine treatment.
D-Cysteine Blocks a Vital Enzyme in Cancer Cells
Through collaboration with Professor Roland Lill’s team at the University of Marburg, researchers identified the mechanism behind D-Cys’s toxicity. The compound inhibits an essential enzyme called NFS1, located in the mitochondria—the cell’s powerhouses.
“NFS1 is crucial for producing iron-sulfur clusters, tiny structures vital for respiration, DNA and RNA synthesis, and maintaining genetic stability,” explained Professor Lill. By blocking NFS1, D-Cys disrupts these processes, leading to reduced respiration, DNA damage, and cell cycle arrest in cancer cells.
Slowing Tumor Growth in Mice
To test its therapeutic potential, researchers administered D-Cys to mice with aggressive mammary tumors. The treatment significantly slowed tumor growth without causing major side effects. “This is a very encouraging result,” said Professor Martinou. “It shows that D-cysteine can be used to specifically target certain cancer cells. However, further studies are needed to determine whether effective and safe doses can be achieved in humans.”
Toward a Simple and Selective Cancer Therapy
If proven safe for clinical use, D-cysteine could represent a simple, innovative, and selective treatment for cancers that overexpress the relevant transporter. Moreover, researchers believe it might also help prevent metastasis, addressing one of the most challenging aspects of cancer progression.
This groundbreaking discovery opens new possibilities for precision oncology, where the natural properties of amino acids can be harnessed to fight cancer more effectively and safely.