Mirror-image cysteine slows cancer growth without harming healthy cells

Scientists have identified a mirror-image version of the amino acid cysteine, known as D-cysteine, that can slow the growth of certain cancers while sparing healthy cells. The molecule targets a specific transporter on cancer cell surfaces, disrupting key metabolic processes inside. In mouse studies, it significantly reduced aggressive breast tumor progression without major side effects.

An international research team from the Universities of Geneva and Marburg has developed a potential cancer therapy using D-cysteine, a rare mirror-image form of the amino acid cysteine. Unlike conventional treatments that often damage healthy tissues, D-cysteine is selectively absorbed by certain cancer cells via a unique surface transporter. Once inside, it inhibits the mitochondrial enzyme NFS1, which is essential for producing iron-sulfur clusters needed for cellular respiration, DNA production, and genetic stability.

The discovery stems from experiments showing that D-cysteine strongly suppresses cancer cell proliferation in lab settings, while healthy cells remain unaffected. "This difference between cancer cells and healthy cells is easily explained: D-Cys is imported into cells via a specific transporter that is present only on the surface of certain cancer cells," said Joséphine Zangari, a PhD student in Jean-Claude Martinou's lab at the University of Geneva and the study's first author.

Further analysis revealed that blocking NFS1 leads to reduced cellular respiration, increased DNA damage, and halted cell division in cancer cells. Collaborating with Roland Lill's team at the University of Marburg, the researchers detailed how this disruption starves cancer cells of vital energy sources. "It blocks an essential enzyme called NFS1, located in the mitochondria -- the cell's 'powerhouses'. This enzyme plays a key role in producing iron-sulfur clusters, small structures that are indispensable for many processes such as cellular respiration, DNA and RNA production, and maintaining genetic integrity," Lill explained.

In vivo tests on mice with aggressive mammary tumors demonstrated promising results: tumor growth slowed substantially, and the animals exhibited no significant adverse effects. "This is a very positive signal -- we now know it's possible to exploit this specificity to target certain cancer cells," noted Jean-Claude Martinou, honorary professor at the University of Geneva. The findings, published in Nature Metabolism in 2025, suggest D-cysteine could offer a selective treatment for cancers expressing high levels of the transporter, potentially aiding in preventing metastasis. Additional human studies are needed to assess safety and dosing.

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