title: Hydrogen sulfide contributes to hypoxia-induced radioresistance on hepatoma cells.
abstract: Growing evidence has demonstrated that, as an endogenous signaling gasotransmitter, hydrogen sulfide (H(2)S) plays an important role in regulating numerous biological functions. The role of H(2)S in hypoxia-induced radioresistance on hepatoma cells was investigated in the present work. Results showed that, when HepG2 cells were maintained in hypoxia circumstances for 4 h, the cellular radioresistance was extensively increased so that the oxygen enhancement ratio of the survival fraction approached 2.68. Under this hypoxic condition, when the cells were treated with DL-propargylglycine (PPG) and aminooxyacetic acid (AOAA), a specific inhibitor of H(2)S synthase of cystathionine-γ-lyase (CSE) and cystathionine-β-synthase (CBS) respectively, radiation responses including cell killing, micronuclei (MN) formation, and caspase-3 activity were significantly enhanced. However, treatment of cells with low concentrations of NaHS (≤ 100 µM) protected cells from these radiation damages. Western bolting assay showed that CSE and CBS were over-expressed in the irradiated hypoxic cells in a dose dependent manner. Moreover, when the hypoxic HepG2 cells were treated with NaHS together with glibenclamide, a specific inhibitor of K(+)(ATP) channels, the role of exogenous H(2)S in radioprotection was partly eliminated. This study demonstrated that H(2)S contributed to hypoxia-induced radioresistance probably via the opening of K(+)(ATP) channels, which suggests that the endogenous H(2)S synthase could be a potential radiotherapeutic target for a hypoxic tumor.
authors.affiliation: Institute of Radiation Medicine, Fudan University, Shanghai, China.
authors.forename: Jianghong
authors.initials: J
authors.lastname: Zhang
authors.forename: Yuexia
authors.initials: Y
authors.lastname: Xie
authors.forename: Yanwu
authors.initials: Y
authors.lastname: Xu
authors.forename: Yan
authors.initials: Y
authors.lastname: Pan
authors.forename: Chunlin
authors.initials: C
authors.lastname: Shao
mesh_terms: D000625:Aminooxyacetic Acid / Q000494:pharmacology; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000532:radiotherapy*; D053148:Caspase 3 / Q000378:metabolism; D015687:Cell Hypoxia / Q000502:physiology; D002470:Cell Survival / Q000528:radiation effects; D003541:Cystathionine beta-Synthase / Q000037:antagonists & inhibitors; D003542:Cystathionine gamma-Lyase / Q000037:antagonists & inhibitors; D056945:Hep G2 Cells; D006801:Humans; D006862:Hydrogen Sulfide / Q000378:metabolism*; D054086:KATP Channels / Q000037:antagonists & inhibitors / Q000378:metabolism; D008113:Liver Neoplasms / Q000378:metabolism* / Q000532:radiotherapy*; D015162:Micronucleus Tests; D011836:Radiation Tolerance / Q000187:drug effects / Q000502:physiology*; D013440:Sulfides / Q000494:pharmacology; D059016:Tumor Microenvironment
chemical_list: D054086:KATP Channels; D013440:Sulfides; D000625:Aminooxyacetic Acid; C505407:CASP3 protein, human; D053148:Caspase 3; D003541:Cystathionine beta-Synthase; D003542:Cystathionine gamma-Lyase; C025451:sodium bisulfide; D006862:Hydrogen Sulfide