Selenium and the selenoprotein thioredoxin reductase in the prevention, treatment and diagnostics of cancer.
Selenium is an essential element that is specifically incorporated as selenocystein into selenoproteins. It is a potent modulator of eukaryotic cell growth with strictly concentration-dependant effects. Lower concentrations are necessary for cell survival and growth, whereas higher concentrations inhibit growth and induce cell death. It is well established that selenium has cancer preventive effects, and several studies also have shown that it has strong anticancer effects with a selective cytotoxicity on malignant drug-resistant cells while only exerting marginal effects on normal and benign cells. This cancer-specific cytotoxicity is likely explained by high affinity selenium uptake dependent on proteins connected to multidrug resistance. One of the most studied selenoproteins in cancer is thioredoxin reductase (TrxR) that has important functions in neoplastic growth and is an important component of the resistant phenotype. Several reports have shown that TrxR is induced in tumor cells and pre-neoplastic cells, and several commonly used drugs interact with the protein. In this review, we summarize the current knowledge of selenium as a potent preventive and tumor selective anticancer drug, and we also discuss the potential of using the expression and modulation of the selenoprotein TrxR in the diagnostics and treatment of cancer.
Selenius
Markus
M
Division of Pathology, Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
Rundlöf
Anna-Klara
AK
Olm
Eric
E
Fernandes
Aristi P
AP
Björnstedt
Mikael
M
D017398:Alternative Splicing; D000975:Antioxidants / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D002986:Clinical Trials as Topic; D019587:Dietary Supplements; D015195:Drug Design; D005091:Exons; D006801:Humans; D009369:Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000517:prevention & control* / Q000628:therapy*; D016877:Oxidants / Q000378:metabolism; D010084:Oxidation-Reduction; D012643:Selenium / Q000378:metabolism* / Q000627:therapeutic use; D013880:Thioredoxin-Disulfide Reductase / Q000235:genetics / Q000378:metabolism*
D000975:Antioxidants; D015415:Biomarkers; D016877:Oxidants; D013880:Thioredoxin-Disulfide Reductase; D012643:Selenium