title: GSH loss per se does not affect neuroblastoma survival and is not genotoxic.
abstract: Depletion of glutathione (GSH) by buthionine sulfoximine (BSO) has been reported to be toxic against some cancer cells and to sensitize many tumours including neuroblastoma (NB) to anticancer drugs. The balance between the production rate of reactive oxygen species (ROS) and the function of GSH affects the intracellular reduction-oxidation status, which is crucial for the regulation of several cellular physiological functions. To assess the role of glutathione in neuroblastoma therapy, the effect of sublethal concentrations of BSO was studied in a panel of neuroblastoma cell lines characterized by different MYCN status. We found that GSH depletion per se not accompanied by ROS overproduction, does not affect cell survival, and is not genotoxic but induces HO-1 expression in GI-ME-N cell line, a representative example of MYCN non-amplified NB cells, having the highest basal levels of GSH among the tested NB lines. These observations might open a novel therapeutic window based on the possibility of modulating the cellular 'activity' of GSH.
authors: G. Gaslini Institute, Gaslini Hospital, I-16148 Genoa, Italy.
authors: Barbara
authors: B
authors: Marengo
authors: Emanuela
authors: E
authors: Balbis
authors: Stefania
authors: S
authors: Patriarca
authors: Chiara
authors: C
authors: De Ciucis
authors: Annalisa
authors: A
authors: Furfaro
authors: Mariapaola
authors: M
authors: Nitti
authors: Umberto Maria
authors: UM
authors: Marinari
authors: Maria Adelaide
authors: MA
authors: Pronzato
authors: Nicola
authors: N
authors: Traverso
authors: Cinzia
authors: C
authors: Domenicotti
mesh_terms: D019328:Buthionine Sulfoximine / Q000494:pharmacology* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D005978:Glutathione / Q000378:metabolism*; D019803:Glutathione Disulfide / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000096:biosynthesis; D006801:Humans; D000071447:N-Myc Proto-Oncogene Protein; D009447:Neuroblastoma / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality*; D009687:Nuclear Proteins / Q000032:analysis; D015513:Oncogene Proteins / Q000032:analysis; D017382:Reactive Oxygen Species
chemical_list: C459801:MYCN protein, human; D000071447:N-Myc Proto-Oncogene Protein; D009687:Nuclear Proteins; D015513:Oncogene Proteins; D017382:Reactive Oxygen Species; D019328:Buthionine Sulfoximine; D051547:Heme Oxygenase-1; D005978:Glutathione; D019803:Glutathione Disulfide