The production of hydrogen sulfide in glioblastoma cell lines

Hydrogen sulfide (H2S) functions as a signaling molecule and a cytoprotectant. The pathway to produce H2S includes cystathionine β-synthase (CBS), cystathionine γ-lyase (CSE), and 3-mercaptopyruvate sulfurtransferase (3MST). 3MST produces H2S from 3-mercaptopyruvate that is provided from l-cysteine and α-ketoglutarate (α-KG) by cysteine aminotransferase (CAT) and from d-cysteine by d-amino acid oxidase (DAO). Recently, a new concept emerges in H2S biology, showing tumor cells upregulate the production of H2S and utilize it to promote tumor growth and chemotherapy resistance. In this study, we investigated the production of H2S in cell lines derived from glioblastoma, the most common- and aggressive-type of brain tumors among adults. Lysates of glioblastoma cells produced H2S from l-cysteine and α-KG. In the absence of α-KG, the production of H2S was significantly decreased, suggesting that H2S production is dependent on the activity of CAT. The production of H2S from l-cysteine and α-KG was correlated with the amount of bound sulfane sulfur, a storage form of H2S. Unlike the l-cysteine pathway, d-cysteine pathway does not operate in the glioblastoma cells. Further investigation will be needed to clarify whether regulation of the l-cysteine pathway changes proliferation and anti-cancer drug resistance of the glioblastoma cells.