Differential effects of selenium on benign and malignant prostate epithelial cells: stimulation of LNCaP cell growth by noncytotoxic, low selenite concentrations.
We examined the hypothesis that nontoxic concentrations of selenium induce apoptosis and growth inhibition selectively in prostate cancer cells but not in benign prostate cells. Nontumorigenic BPH-1 prostate epithelial cells, androgen-sensitive LNCaP, and androgen-independent PC-3 prostate cancer cells were exposed to sodium selenite at 1 to 10 micromol/l for 24 to 72 h. Cell proliferation, viability, and apoptosis were assessed by MTT assay, trypan blue exclusion, flow cytometry, DNA laddering, and caspase activation. BPH-1 cells were more sensitive for cytotoxic selenium effects than malignant prostate cells, whereas LNCaP cells were more sensitive than PC-3 cells. At noncytotoxic selenium concentrations, there was no apoptosis in BPH-1 and PC-3 cells and no growth inhibition of LNCaP and BPH-1 cells. PC-3 cells were refractory to apoptosis induction but were growth inhibited at noncytotoxic concentrations. LNCaP cells were growth stimulated at 1 micromol/l and sensitive to apoptosis induction at higher noncytotoxic concentrations. Thus, noncytotoxic selenite concentrations did not induce growth inhibition or apoptosis selectively in prostate cancer cells. Growth stimulation of LNCaP cells by low concentrations suggests the possibility of adverse effects of selenium supplementation on hormone sensitive prostate cancer, whereas inhibition of PC-3 cell proliferation at noncytotoxic concentrations suggests potential benefit of selenium in advanced prostate cancer.
Kandaş
Nur Ozten
NO
Department of Pathology, University of Illinois at Chicago, 840 South Wood Street, Chicago, IL 60612, USA.
Randolph
Carla
C
Bosland
Maarten C
MC
D000728:Androgens / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects; D006801:Humans; D008297:Male; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011470:Prostatic Hyperplasia / Q000473:pathology; D011471:Prostatic Neoplasms / Q000201:enzymology / Q000473:pathology*; D012333:RNA, Messenger / Q000032:analysis; D012643:Selenium / Q000009:adverse effects; D018038:Sodium Selenite / Q000008:administration & dosage*; D013880:Thioredoxin-Disulfide Reductase / Q000235:genetics / Q000378:metabolism
D000728:Androgens; D012333:RNA, Messenger; D013880:Thioredoxin-Disulfide Reductase; D011065:Poly(ADP-ribose) Polymerases; D053148:Caspase 3; D012643:Selenium; D018038:Sodium Selenite