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

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