Extracellular thiol-assisted selenium uptake dependent on the x c − cystine transporter explains the cancer-specific cytotoxicity of selenite

• DOI: 10.1073/pnas.0902204106
• Publication Date: 2009-06-23T02:04:42Z
• Authors: Eric Olm; Aristi P. Fernandes; Christina Hebert; Anna-Klara Rundlöf; Erik H. Larsen; Olof Danielsson; Mikael Björnstedt
• Keywords: 0301 basic medicine; 0303 health sciences; Lung Neoplasms; Amino Acid Transport System y+; Cell Death; Glutathione; Models, Biological; Antiporters; 3. Good health; Selenium; 03 medical and health sciences; Sodium Selenite; Drug Resistance, Neoplasm; Cell Line, Tumor; Organoselenium Compounds; Cystine; Humans; ATP Binding Cassette Transporter, Subfamily B, Member 1; Sulfhydryl Compounds; Extracellular Space; Oxidation-Reduction

The selenium salt selenite (SeO 3 2− ) is cytotoxic in low to moderate concentrations, with a remarkable specificity for cancer cells resistant conventional chemotherapy. Our data show that uptake and accumulation, rather than intracellular events, are crucial the specific cytotoxicity observed cells. We depends on extracellular reduction, environment key factor cytotoxicity. reduction mediated by cysteine, efficacy determined of cystine x c − antiporter secretion cysteine multidrug resistance proteins, both which frequently overexpressed This mechanism provides molecular evidence existence an inverse relationship between chemotherapy sensitivity cytotoxicity, highlights great therapeutic potential treating multidrug-resistant cancer.