Hydrogen Sulfide (H₂S): As a Potent Modulator and Therapeutic Prodrug in Cancer

Hydrogen sulfide (H₂S) is an endogenous gaseous molecule present in all living organisms that has been traditionally studied for its toxicity. Interestingly, increased understanding of H₂S effects in organ physiology has recently shown its relevance as a signalling molecule, with potentially important implications in variety of clinical disorders, including cancer. H₂S is primarily produced in mammalian cells under various enzymatic pathways are target of intense research biological mechanisms, and therapeutic effects of H₂S. Herein, we describe the physiological and biochemical properties of H₂S, the enzymatic pathways leading to its endogenous production and its catabolic routes. In addition, we discuss the role of currently known H₂S-releasing agents, or H₂S donors, including their potential as therapeutic tools. Then we illustrate the mechanisms known to support the pleiotropic effects of H₂S, with a particular focus on persulfhydration, which plays a key role in H₂S-mediating signalling pathways. We then address the paradoxical role played by H₂S in tumour biology and discuss the potential of exploiting H₂S levels as novel cancer biomarkers and diagnostic tools. Finally, we describe the most recent preclinical applications focused on assessing the anti-cancer impact of most common H₂S-releasing compounds. While the evidence in favour of H₂S as an alternative cancer therapy in the field of translational medicine is yet to be clearly provided, application of H₂S is emerging as a potent anticancer therapy in preclinical trails.