GSH loss per se does not affect neuroblastoma survival and is not genotoxic.
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.
Marengo
Barbara
B
G. Gaslini Institute, Gaslini Hospital, I-16148 Genoa, Italy.
Balbis
Emanuela
E
Patriarca
Stefania
S
De Ciucis
Chiara
C
Furfaro
Annalisa
A
Nitti
Mariapaola
M
Marinari
Umberto Maria
UM
Pronzato
Maria Adelaide
MA
Traverso
Nicola
N
Domenicotti
Cinzia
C
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
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