title: Selenite induces apoptosis in sarcomatoid malignant mesothelioma cells through oxidative stress.
abstract: Malignant mesothelioma cells differentiate into sarcomatoid or epithelioid phenotypes. The sarcomatoid cell type is more resistant to chemotherapy and gives a worse prognosis. We have investigated whether selenite alone and in combination with doxorubicin induced apoptosis in variously differentiated mesothelioma cells. Selenite in concentrations that could potentially be administered to patients strongly inhibited the growth of the sarcomatoid mesothelioma cells (IC50 = 7.5 microM), whereas epithelioid cells were more sensitive to doxorubicin. Benign mesothelial cells remained largely unaffected. Selenite potentiated doxorubicin treatment. Apoptosis was the dominating mode of cell death. The toxicity of selenite was mediated by oxidative stress. Furthermore the activity of the thioredoxin system was directly dependent on the concentration of selenite. This offers a possible mechanism of action of selenite treatment. Our findings suggest that selenite is a promising new drug for the treatment of malignant mesothelioma.
authors.affiliation: Department of Laboratory Medicine, Karolinska University Hospital, F-46, Karolinska Institutet, S-141 86 Huddinge, Stockholm, Sweden.
authors.forename: Gustav
authors.initials: G
authors.lastname: Nilsonne
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: Sun
authors.forename: Christina
authors.initials: C
authors.lastname: Nyström
authors.forename: Anna-Klara
authors.initials: AK
authors.lastname: Rundlöf
authors.forename: Aristi
authors.initials: A
authors.lastname: Potamitou Fernandes
authors.forename: Mikael
authors.initials: M
authors.lastname: Björnstedt
authors.forename: Katalin
authors.initials: K
authors.lastname: Dobra
mesh_terms: D000230:Adenocarcinoma; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D005979:Glutathione Peroxidase / Q000378:metabolism; D006801:Humans; D008654:Mesothelioma / Q000473:pathology*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D018038:Sodium Selenite / Q000633:toxicity*; D013438:Sulfhydryl Compounds / Q000378:metabolism
chemical_list: D013438:Sulfhydryl Compounds; D005979:Glutathione Peroxidase; D018038:Sodium Selenite