Hydrogen Sulfide-Synthesizing Enzymes Are Altered in a Case of Oral Cavity Mucoepidermoid Carcinoma

Abstract

Mucoepidermoid carcinoma (MEC) is the most common malignant epithelial neoplasm of the salivary glands. MECs of the mouth floor are rare, with only a few cases reported. Here we report a MEC of the mouth floor in a 55-year-old woman. Since several studies have shown that hydrogen sulfide (H 2 S)-synthesizing enzymes are often increased in malignant tumors compared to benign counterpart tissues, we used western blotting to compare the protein levels of cystathionine-β-synthase (CBS), cystathionine γ-lyase (CSE), and 3-mercaptopyruvate sulfurtransferase (3-MST) in a mouth floor MEC to adjacent benign oral mucosae. We also used high-performance liquid chromatography to quantify possible differences in tissue sulfur fraction concentrations between the two biopsy types. Last, we used western blotting to examine nicotinamide phosphoribosyl transferase (Nampt), mitoNEET, and phospho-ser727-Stat3 levels in the biopsies. We found that all the proteins and phospho-ser727-Stat3 are increased in the MEC compared to benign mucosae. Interestingly, free H 2 S levels, acid-labile, and the sulfane sulfur factions were essentially the same between the MEC and benign tissue. Although limited to a single and unusual tumor type, to our knowledge this is only the third time H 2 S concentrations were directly quantified inside a human tumor. Last, our results replicate those of two previous studies where the H 2 S-synthesizing enzymes are increased in a malignant tumor, while free H 2 S is either not increased or only slightly increased, suggesting that malignant tumors rapidly metabolize H 2 S as part of tumor maintenance and growth.