title: Hydrogen sulfide (H2S)/cystathionine γ-lyase (CSE) pathway contributes to the proliferation of hepatoma cells.
abstract: Hydrogen sulfide (H2S)/cystathionine γ-lyase (CSE) pathway has been demonstrated to play vital roles in physiology and pathophysiology. However, its role in tumor cell proliferation remains largely unclear. Here we found that CSE over-expressed in hepatoma HepG2 and PLC/PRF/5 cells. Inhibition of endogenous H2S/CSE pathway drastically decreased the proliferation of HepG2 and PLC/PRF/5 cells, and it also enhanced ROS production and mitochondrial disruption, pronounced DNA damage and increased apoptosis. Moreover, this increase of apoptosis was associated with the activation of p53 and p21 accompanied by a decreased ratio of Bcl-2/Bax and up-regulation of phosphorylated c-Jun N-terminal kinase (JNK) and caspase-3 activity. In addition, the negative regulation of cell proliferation by inhibition of H2S/CSE system correlated with the blockage of cell mitogenic and survival signal transduction of epidermal growth factor receptor (EGFR) via down-regulating the extracellular-signal-regulated kinase 1/2 (ERK1/2) activation. These results demonstrate that H2S/CSE and its downstream pathway contribute to the proliferation of hepatoma cells, and inhibition of this pathway strongly suppress the excessive growth of hepatoma cells by stimulating mitochondrial apoptosis and suppressing cell growth signal transduction.
authors.affiliation: Institute of Radiation Medicine, Fudan University, No. 2094 Xie-Tu Road, Shanghai 200032, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Pan
authors.affiliation: Institute of Radiation Medicine, Fudan University, No. 2094 Xie-Tu Road, Shanghai 200032, China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Ye
authors.affiliation: Institute of Radiation Medicine, Fudan University, No. 2094 Xie-Tu Road, Shanghai 200032, China.
authors.forename: Dexiao
authors.initials: D
authors.lastname: Yuan
authors.affiliation: Institute of Radiation Medicine, Fudan University, No. 2094 Xie-Tu Road, Shanghai 200032, China.
authors.forename: Jianghong
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Institute of Radiation Medicine, Fudan University, No. 2094 Xie-Tu Road, Shanghai 200032, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Bai
authors.affiliation: Institute of Radiation Medicine, Fudan University, No. 2094 Xie-Tu Road, Shanghai 200032, China. Electronic address: clshao@shmu.edu.cn.
authors.forename: Chunlin
authors.initials: C
authors.lastname: Shao
mesh_terms: D017209:Apoptosis; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism; D049109:Cell Proliferation; D002470:Cell Survival; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D003542:Cystathionine gamma-Lyase / Q000378:metabolism*; D004249:DNA Damage; D056945:Hep G2 Cells; D006801:Humans; D006862:Hydrogen Sulfide / Q000378:metabolism*; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D020935:MAP Kinase Signaling System; D008930:Mitochondria, Liver / Q000378:metabolism / Q000473:pathology; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: C494826:BAX protein, human; C000595707:BCL2 protein, human; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D019253:Proto-Oncogene Proteins c-bcl-2; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048670:MAP Kinase Kinase 4; C505407:CASP3 protein, human; D053148:Caspase 3; D003542:Cystathionine gamma-Lyase; D006862:Hydrogen Sulfide
keywords: Apoptosis; EGFR; ERK1/2; H(2)S/CSE; Hepatoma cells; Proliferation