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  • Title: Redox-mediated effects of selenium on apoptosis and cell cycle in the LNCaP human prostate cancer cell line.
    Author: Zhong W, Oberley TD.
    Journal: Cancer Res; 2001 Oct 01; 61(19):7071-8. PubMed ID: 11585738.
    Abstract:
    The effects of selenium exposure were studied in LNCaP human prostate cancer cells, and this same cell line adapted to selenium over 6 months to compare acute versus chronic effects of sodium selenite, the latter most closely resembling human clinical trials on the effects of selenium in cancer prevention and therapy. Our results demonstrated that oxidative stress was induced by sodium selenite at high concentrations in both acute and chronic treatments, but outcomes were different. After acute exposure to selenite, cells exhibited mitochondrial injury and cell death, mainly apoptosis. After chronic exposure to selenite, cells showed growth inhibition caused by cell cycle arrest, increased numbers of mitochondria and levels of mitochondrial enzymes, and only minimal induction of apoptosis. Immunoblotting analysis revealed that multiple proteins were up-regulated by chronic exposure to selenite. Among them, only up-regulation of manganese superoxide dismutase and the cyclin-dependent kinase inhibitor p21(Waf1/Cip1), proteins known to be redox sensitive and to have cell cycle regulatory functions, correlated with cell growth inhibition. Our results in selenite-adapted cells suggest that selenium may exert its effects in human prostate cancer cells by altering intracellular redox state, which subsequently results in cell cycle block.
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