Cystine depletion

Cystine depletion refers to the reduction or removal of extracellular cystine, the oxidized dimeric form of the amino acid cysteine. This process is not a molecular target itself but rather a therapeutic strategy aimed at disrupting cellular redox homeostasis. In cancer biology, particularly pancreatic ductal adenocarcinoma, tumor cells are highly dependent on imported cyst(e)ine for synthesizing glutathione and coenzyme A—key molecules that protect against reactive oxygen species. Depleting extracellular cyst(e)in(e), either genetically by targeting transporters like system xC– (SLC7A11 subunit) or pharmacologically with agents such as engineered enzymes like cyst(e)inase, induces ferroptosis—a form of iron-dependent non-apoptotic cell death characterized by lipid peroxidation—selectively in tumor cells while sparing normal tissue under certain conditions. In obesity research, dietary restriction of cysteine leads to rapid weight loss through global metabolic reprogramming without major adverse effects on vital functions in animal models. However, "cystine depletion" is not a canonical protein/receptor/enzyme target but rather describes an intervention strategy affecting multiple pathways.[1][2][3]

Other names

Cysteine depletioncyst(e)inase-induced cystine/cysteine depletionamino acid deprivation (cystine/cysteine)

- Induction of ferroptosis by reducing intracellular glutathione and coenzyme A levels through limiting cysteine availability[1][3][6]\n- Triggering oxidative stress responses and metabolic reprogramming via amino acid deprivation[2]