The role of survivin and Bcl-2 in zinc-induced apoptosis in prostate cancer cells.
OBJECTIVE
To study the effects of zinc treatment on the gene expression levels of survivin and Bcl-2 in prostate cancer cells.


METHODS
The effects of zinc exposure on apoptosis were assessed using two human prostate cancer cell lines, LNCaP and PC-3. Zinc-induced apoptosis was measured by Annexin V staining. The direct effect of zinc on the expression levels of zinc transporters (ZnT-1 and ZnT-4) and apoptosis-related genes (Bax, Bcl-2, and survivin) was determined by RT-PCR analysis.


RESULTS
When LNCaP and PC-3 cells were exposed to various concentrations of zinc sulfate for 48 hors, their growth was inhibited in a dose-dependent manner. The levels of zinc in both cell lines treated with zinc sulfate for 24 hours were higher than in untreated cells. Exposure to zinc induced apoptosis and necrosis in LNCaP and PC-3 cells. Apoptosis became more extensive as the treatment time with zinc increased. There was a significant increase in the gene expression levels of ZnT-1 and ZnT-4 in both cell lines treated with zinc sulfate compared with untreated cells. The expression of Bax mRNA was up-regulated, while the expression of Bcl-2 and survivin were decreased in both cell lines following zinc treatment.


CONCLUSIONS
Exposure to zinc sulfate in human prostate cancer cells increased intracellular levels of zinc, which resulted in increased apoptosis. The apoptogenic effect of elevated concentration of zinc could be due either to increased expression of zinc transporters and increased levels of Bax or decreased Bcl-2 and survivin expression.
Ku
Ja Hyeon
JH
Department of Urology, Seoul National University Hospital, Seoul, Korea.
Seo
Soo Yeon
SY
Kwak
Cheol
C
Kim
Hyeon Hoe
HH
D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D027682:Cation Transport Proteins / Q000235:genetics; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics*; D008297:Male; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000077022:Survivin; D013997:Time Factors; D015032:Zinc / Q000378:metabolism / Q000494:pharmacology*; D051028:bcl-2-Associated X Protein / Q000235:genetics
C494826:BAX protein, human; C107489:BIRC5 protein, human; D027682:Cation Transport Proteins; D051034:Inhibitor of Apoptosis Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; C498299:SLC30A1 protein, human; C491597:SLC30A4 protein, human; D000077022:Survivin; D051028:bcl-2-Associated X Protein; D015032:Zinc