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The role of survivin and Bcl-2 in zinc-induced apoptosis in prostate cancer cells☆

  • Ja Hyeon Ku, M.D., Ph.D.

      Affiliations

    • Department of Urology, Seoul National University Hospital, Seoul, Korea
    • ,
  • Soo Yeon Seo, B.Sc.

      Affiliations

    • Department of Urology and Clinical Research Institute, Seoul National University Hospital, Seoul, Korea
    • ,
  • Cheol Kwak, M.D., Ph.D.

      Affiliations

    • Department of Urology, Seoul National University Hospital, Seoul, Korea
    • ,
  • Hyeon Hoe Kim, M.D., Ph.D.

      Affiliations

    • Department of Urology, Seoul National University Hospital, Seoul, Korea
    • Corresponding Author InformationCorresponding author. Tel.: +82-2-2072-2425; fax: +82-2-742-4665

Received 22 April 2010; received in revised form 29 May 2010; accepted 5 June 2010. published online 07 September 2010.
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Abstract 

Objectives:

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

Materials and 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.

Keywords: Prostate cancer, Zinc, Bcl-2, Survivin, Apoptosis

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☆ This work was supported by grant no. 04-2008-077-0 from the SNUH Research Fund.

PII: S1078-1439(10)00158-4

doi:10.1016/j.urolonc.2010.06.001

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