N -Acetylcysteine Serves as Substrate of 3-Mercaptopyruvate Sulfurtransferase and Stimulates Sulfide Metabolism in Colon Cancer Cells

• Published in: Cells (Basel, Switzerland) Vol. 8; no. 8; p. 828
• Main Authors: Zuhra, Karim, Tomé, Catarina S, Masi, Letizia, Giardina, Giorgio, Paulini, Giulia, Malagrinò, Francesca, Forte, Elena, Vicente, João B, Giuffrè, Alessandro
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 04.08.2019; MDPI
• Subjects: 3-Mercaptopyruvate sulfurtransferase; Acetylcysteine; Acetylcysteine - pharmacology; Acids; Antioxidants; Biosynthesis; Cancer therapies; Cell Line, Tumor; Cell proliferation; Colon cancer; Colonic Neoplasms - metabolism; Colorectal cancer; Energy Metabolism; enzymatic activity assays; Enzymes; Free Radical Scavengers - pharmacology; Homeostasis; Humans; Hydrogen sulfide; Hydrogen Sulfide - metabolism; Intracellular levels; Localization; Mammals; Melanoma; Metabolism; Microbiota; Mitochondria; Mitochondria - metabolism; Oxidation; Oxidative stress; Oxidoreductases Acting on Sulfur Group Donors - metabolism; Phosphorylation; Polyclonal antibodies; protein expression levels; Proteins; Quinone oxidoreductase; sulfane sulfur species; Sulfur; Sulfurtransferase; Sulfurtransferases - metabolism; United States > US; colorectal cancer; protein expression levels; hydrogen sulfide; enzymatic activity assays; antioxidants; sulfane sulfur species
• ISSN: 2073-4409; 2073-4409
• DOI: 10.3390/cells8080828

Hydrogen sulfide (H S) 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 H S, generate sulfane sulfur species such as persulfides and polysulfides, currently recognized as mediating some of the H S biological effects. Reprogramming of H S metabolism was reported to support cellular proliferation and energy metabolism in cancer cells. As oxidative stress is a cancer hallmark and -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 H S 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 H S 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 H S metabolism and that NAC can serve as a substrate for human MST.