Selenium-induced cytotoxicity of human leukemia cells: interaction with reduced glutathione.
Selenium exists in a number of forms with differing valence states, some of which have shown antitumor activity. We studied the tumoricidal activity of four currently available selenium forms against a human leukemia cell line and exploited the differences among them to investigate the mechanism of antitumor action. Only selenocystine and sodium selenite showed antitumor activity, and these were also the only compounds which demonstrated significant redox chemistry, including depletion of cellular glutathione, stimulation of glutathione reductase, and stimulation of oxygen consumption. The interaction of these two compounds with glutathione suggests an intriguing potential role for them in cancer therapy.
D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003553:Cystine / Q000031:analogs & derivatives / Q000633:toxicity; D005978:Glutathione / Q000378:metabolism*; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D006801:Humans; D007942:Leukemia, Experimental / Q000473:pathology / Q000503:physiopathology; D009249:NADP; D016566:Organoselenium Compounds; D010101:Oxygen Consumption / Q000187:drug effects; D020887:Selenious Acid; D012643:Selenium / Q000633:toxicity*
D016566:Organoselenium Compounds; C009226:selenocystine; D003553:Cystine; D009249:NADP; D005979:Glutathione Peroxidase; D005980:Glutathione Reductase; D020887:Selenious Acid; D005978:Glutathione; D012643:Selenium