Cysteine Metabolism as a Central Metabolic Driver and Selenocompounds as Therapeutic Agents

Amino acid metabolism plays a vital role in both health and disease, supporting essential processes such as protein synthesis, signaling, energy production, and epigenetic regulation. Among the amino acids, cysteine is particularly notable due to its sulfur-containing thiol group, which is crucial for antioxidant regulation and various cellular functions. Cysteine's biological significance extends to its involvement in maintaining redox homeostasis, synthesizing key molecules like glutathione (GSH), and producing hydrogen sulfide (H₂S), a molecule that acts as both an antioxidant and a signaling agent. Furthermore, cysteine contributes to energy production and serves as a precursor for several post-translational modifications.In cancer, metabolic reprogramming leads to a dependence on specific nutrients, with cysteine metabolism emerging as a promising therapeutic target. This chapter will explore cysteine's dual role as both a sulfur and carbon source, as well as its antioxidant properties. Strategies to exploit cysteine dependency, particularly through the inhibition of xCT-a key transporter involved in cysteine uptake-will be discussed, highlighting its potential to induce ferroptosis and reduce tumor growth. The search for safer, less toxic inhibitors has turned to seleno-compounds, which can inhibit xCT while promoting selenium uptake and ferroptosis. Selenium's multifaceted role in cancer therapy, including its effects on redox balance, apoptosis, and immune modulation, further underscores its therapeutic potential. Advances in nanoparticle-based drug delivery systems for selenium-based therapies will also be presented, showing promise in enhancing targeted treatment, reducing off-target effects, and maximizing therapeutic efficacy. Overall, these advancements in selenium-based therapies, combined with ongoing research into cysteine metabolism, provide a strong foundation for the development of novel, metabolism-based anti-cancer strategies.