title: Endogenous Hydrogen Sulfide Enhances Cell Proliferation of Human Gastric Cancer AGS Cells.
abstract: Hydrogen sulfide (H2S), the third gasotransmitter, is endogenously generated by certain H2S synthesizing enzymes, including cystathionine-γ-lyase (CSE) and cystathionine-β-synthase (CBS) from L-cysteine in the mammalian body. Several studies have shown that endogenous and exogenous H2S affects the proliferation of cancer cells, although the effects of H2S appear to vary with cell type, being either promotive or suppressive. In the present study, we determined whether endogenously formed H2S regulates proliferation in human gastric cancer AGS cells. CSE, but not CBS, was expressed in AGS cells. CSE inhibitors, DL-propargylglycine (PPG) and β-cyano-L-alanine (BCA), significantly suppressed the proliferation of AGS cells in a concentration-dependent manner. CSE inhibitors did not increase lactate dehydrogenase (LDH) release in the same concentration range. The inhibitory effects of PPG and BCA on cell proliferation were reversed by repetitive application of NaHS, a donor of H2S. Interestingly, nuclear condensation and fragmentation were detected in AGS cells treated with PPG or BCA. These results suggest that endogenous H2S produced by CSE may contribute to the proliferation of gastric cancer AGS cells, most probably through anti-apoptotic actions.
authors.affiliation: Laboratory of Pharmacology and Pathophysiology, Faculty of Pharmacy, Kindai University.
authors.forename: Fumiko
authors.initials: F
authors.lastname: Sekiguchi
authors.forename: Teruki
authors.initials: T
authors.lastname: Sekimoto
authors.forename: Ayaka
authors.initials: A
authors.lastname: Ogura
authors.forename: Atsufumi
authors.initials: A
authors.lastname: Kawabata
mesh_terms: D000409:Alanine / Q000031:analogs & derivatives / Q000494:pharmacology; D000480:Alkynes / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003542:Cystathionine gamma-Lyase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D006801:Humans; D006862:Hydrogen Sulfide / Q000378:metabolism*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D013274:Stomach Neoplasms / Q000378:metabolism*; D013440:Sulfides / Q000494:pharmacology
chemical_list: D000480:Alkynes; D013440:Sulfides; C009055:propargylglycine; C004631:3-cyanoalanine; D007770:L-Lactate Dehydrogenase; D003542:Cystathionine gamma-Lyase; C025451:sodium bisulfide; D000409:Alanine; D005998:Glycine; D006862:Hydrogen Sulfide