Selenium effects on prostate cell growth

Epidemiological and clinical data suggest that selenium may prevent prostat e cancer, but the biological effects of selenium on normal or malignant pro state cells are not well known. We evaluated the effects of sodium selenite (Na2SeO3,) or l-selenomethionine (SeMet) on monolayer and anchorage-indepe ndent growth in a series of normal primary prostate cultures (epithelial, s tromal, and smooth muscle) and prostate cancer cell lines (LNCaP, PC-3, and DU145). We observed differential, dose-dependent growth inhibition and apo ptosis within prostate cancer cells (compared with normal prostate cells) t reated with 1-500 muM of Na2SeO3 or SeMet. Na2SeO3 more potently inhibited growth at any given concentration. The androgen-responsive LNCaP cells were the most sensitive to selenium growth suppression (IC50 at 72 h for Na2SeO 3 and SeMet were 0.2 and 1.0 muM, respectively). Growth of the primary pros tate cells virtually was not suppressed (IC50 at 72 h for Na2SeO3 and SeMet were 22-38 and >500 muM, respectively), We also observed that DNA condensa tion and DNA fragmentation (terminal deoxynucleotidyltransferase dUTP nick end labeling/fluorescence-activated cell sorting) were elevated in selenium -treated cells and that activated caspase-3 colocalized with terminal deoxy nucleotidyltransferase dUTP nick end labeling-stained cells by immunofluore scence, Higher basal poly(ADP-ribose) polymerase (PARP) expression levels a nd PARP cleavage (a substrate for caspase-3) were observed during apoptosis in tumor cells, compared with normal cells. Selective tumor cell death was associated with an increase in sub-G(0)-G(1) cells after propidium iodide staining and fluorescence-activated cell sorting analysis. SeMet caused an increase in arrest in the G(2)-M phase of the cell cycle selectively in can cer cells. Inhibition of cancer cell growth by SeMet was associated with ph osphorylation of P-Tyr15-p34/cdc2, which caused growth arrest in the G(2)-M phase. Anchorage-independent growth of prostate cancer cells in soft agar was sensitive to selenium, Our results suggest that Na2SeO3 is the more pot ent inducer of apoptosis in normal and cancer prostate cells. Our SeMet res ults involving PARP and G(2)-M cell-cycle arrest (cited above) indicate tha t SeMet selectively induces apoptosis in cancer but not primary cells of th e human prostate. Our overall findings are relevant to the molecular mechan isms of selenium actions on prostate carcinogenesis and help demonstrate th e selective, dose-dependent effects of selenium (especially SeMet) on prost ate cancer cell death and growth inhibition.