Abstract
Hydrogen sulfide (H2S) is an endogenously produced signaling molecule. The enzymes 3-mercaptopyruvate sulfurtransferase (MST), partly localized in mitochondria, and the inner mitochondrial membrane-associated sulfide:quinone oxidoreductase (SQR), besides being respectively involved in the synthesis and catabolism of H2S, generate sulfane sulfur species such as persulfides and polysulfides, currently recognized as mediating some of the H2S biological effects. Reprogramming of H2S metabolism was reported to support cellular proliferation and energy metabolism in cancer cells. As oxidative stress is a cancer hallmark and N-acetylcysteine (NAC) was recently suggested to act as an antioxidant by increasing intracellular levels of sulfane sulfur species, here we evaluated the effect of prolonged exposure to NAC on the H2S metabolism of SW480 colon cancer cells. Cells exposed to NAC for 24 h displayed increased expression and activity of MST and SQR. Furthermore, NAC was shown to: (i) persist at detectable levels inside the cells exposed to the drug for up to 24 h and (ii) sustain H2S synthesis by human MST more effectively than cysteine, as shown working on the isolated recombinant enzyme. We conclude that prolonged exposure of colon cancer cells to NAC stimulates H2S metabolism and that NAC can serve as a substrate for human MST.
Highlights
Hydrogen sulfide (H2 S) is an endogenously produced signaling molecule involved in the regulation of several physiological processes, such as blood flow, inflammation, neurotransmission, apoptosis, redox homeostasis, energy metabolism and stress response [1,2,3]
Ezerina et al proposed that NAC-derived Cys enhances mitochondrial levels of sulfane sulfur species and suggested that these species are the actual mediators of the antioxidants effects of NAC [62]
By combining work on the SW480 cell line and on recombinant human mercaptopyruvate sulfurtransferase (MST), we observed that NAC promotes increased expression and activity of MST and sulfide:quinone oxidoreductase (SQR), both involved in the production of sulfane sulfur species, but is an effective substrate for MST
Summary
Hydrogen sulfide (H2 S) is an endogenously produced signaling molecule involved in the regulation of several physiological processes, such as blood flow, inflammation, neurotransmission, apoptosis, redox homeostasis, energy metabolism and stress response [1,2,3]. Targeting the ROS signaling pathways and redox mechanisms involved in cancer development was suggested as a potential strategy to prevent both cancer formation and the adverse effects of antitumoral drugs [50]. Ezerina et al proposed that NAC-derived Cys enhances mitochondrial levels of sulfane sulfur species and suggested that these species are the actual mediators of the antioxidants effects of NAC [62]. By combining work on the SW480 cell line and on recombinant human MST, we observed that NAC promotes increased expression and activity of MST and SQR, both involved in the production of sulfane sulfur species, but is an effective substrate for MST
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
