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- W2804981637 abstract "The cancer-preventive mechanism of selenium should address the way low concentrations of selenometabolites react with cellular targets without being diffused from the sites of generation, the way selenium selectively kills tumor cells, and the intriguing U-shaped curve that is seen with dietary supplementation of selenium and cancer prevention. Protein kinase C (PKC), a receptor for tumor promoters, is well suited for this mechanism. Due to the catalytic redox cycle, low concentrations of methylselenol, a postulated active metabolite of selenium, react with the tumor-promoting lipid hydroperoxide bound to PKC to form methylseleninic acid (MSA), which selectively reacts with thiol residues present within the vicinity of the PKC catalytic domain to inactivate it. Given that lipid hydroperoxide levels are high in promoting cells, PKC inactivation selectively leads to death in these cells. A biphasic effect of MSA in inducing cell death was observed in certain prostate cancer cell lines; lower concentrations of MSA induced cell death, while higher concentrations failed to do so. Lower concentrations of selenium inactivate more sensitive antiapoptotic isoenzymes of PKC (ε and α), sparing less sensitive proapoptotic isoenzymes (PKCδ and PKCζ). Higher concentrations of selenium also inactivate proapoptotic isoenzymes and consequently make tumor cells resistant to apoptosis. Due to a high-affinity binding of thioredoxin to the PKC catalytic domain, this thiol oxidation is explicitly reversed by thioredoxin reductase (TXNRD), a selenoprotein. Therefore, overexpression of TXNRD in advanced tumor cells could make them resistant to selenium-induced death. Conceivably, this mechanism, at least in part, explains why selenium prevents cancer only in certain cases." @default.
- W2804981637 created "2018-06-01" @default.
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- W2804981637 date "2018-11-01" @default.
- W2804981637 modified "2023-09-30" @default.
- W2804981637 title "Redox regulation of protein kinase C by selenometabolites and selenoprotein thioredoxin reductase limits cancer prevention by selenium" @default.
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- W2804981637 doi "https://doi.org/10.1016/j.freeradbiomed.2018.05.062" @default.
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