title: MIBG causes oxidative stress and up-regulation of anti-oxidant enzymes in the human neuroblastoma cell line SK-N-BE(2c).
abstract: We report the effects of meta-iodobenzylguanidine (MIBG), a neuroblastoma-seeking agent, on cell proliferation and several oxidative stress-related parameters in the human neuroblastoma cell line SK-N-BE(2c). MIBG inhibited the proliferation of this cell line in micromolar concentrations. Measurements of the malondialdehyde (MDA) concentrations (a measure of the extent of lipid peroxidation) of cells treated with MIBG showed that increasing concentrations of MIBG led to an increase in MDA levels of the cells. This effect was most pronounced after one day of cellular exposure to MIBG and disappeared after 3 days. Disappearance of the elevated MDA levels caused by MIBG is probably the result of increased activity of the H2O2 detoxifying enzymes, catalase and glutathion peroxidase (GPx). The catalase- and GPx-enzyme activity of cells exposed to MIBG steadily increased with time, reaching a maximum after 4 days. Oxidative stress caused by MIBG thus at first leads to cellular damage (lipid peroxidation) but over a longer period does not lead to decreased proliferation rate of the cells, most likely because of cellular adaptation to increased oxidative stress by up-regulation of the H2O2 detoxifying enzymes catalase and GPx.
authors.affiliation: Academic Medical Centre, Department of Paediatrics, Amsterdam, The Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: Cornelissen
authors.forename: A B
authors.initials: AB
authors.lastname: Van Kuilenburg
authors.forename: P A
authors.initials: PA
authors.lastname: Voûte
authors.forename: A H
authors.initials: AH
authors.lastname: Van Gennip
mesh_terms: D019797:3-Iodobenzylguanidine; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000378:metabolism*; D002374:Catalase / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D005979:Glutathione Peroxidase / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D007462:Iodobenzenes / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects; D008315:Malondialdehyde / Q000378:metabolism; D009447:Neuroblastoma / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D000975:Antioxidants; D007462:Iodobenzenes; D019797:3-Iodobenzylguanidine; D008315:Malondialdehyde; D006861:Hydrogen Peroxide; D002374:Catalase; D005979:Glutathione Peroxidase