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Antiproliferative effects of zinc-citrate compound on hormone refractory prostate cancer

  • Original Article
  • Prostate Cancer
  • Published:
Chinese Journal of Cancer Research

Abstract

Objective

To investigate the antiproliferative effects of zinc-citrate compound on hormone refractory prostate cancer (HRPC).

Methods

HRPC cell line (DU145) and normal prostate cell line (RWPE-1) were treated with zinc, citrate and zinc-citrate compound at different time intervals and concentrations to investigate the effect of zinc-citrate compound. Mitochondrial (m)-aconitase activity was determined using aconitase assay. DNA laddering analysis was performed to investigate apoptosis of DU145 cells. Molecular mechanism of apoptosis was investigated by Western blot analysis of P53, P21waf1, Bcl-2, Bcl-xL and Bax, and also caspase-3 activity analysis.

Results

Treatment with zinc-citrate compound resulted in a time- and dose-dependent decrease in cell number of DU145 cells in comparison with RWPE-1. M-aconitase activity was significantly decreased. DNA laddering analysis indicated apoptosis of DU145 cells. Zinc-citrate compound increased the expression of P21waf1 and P53, and reduced the expression of Bcl-2 and Bcl-xL proteins but induced the expression of Bax protein. Zinc-citrate compound induced apoptosis of DU145 cells by activation of the caspase-3 pathway.

Conclusion

Zinc-citrate compound can induce apoptotic cell death in DU145, by caspase-3 activation through up-regulation of apoptotic proteins and down-regulation of antiapoptotic proteins.

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References

  1. Grönberg H. Prostate cancer epidemiology. Lancet 2003; 361:859–864.

    Article  PubMed  Google Scholar 

  2. Moul JW. Variables in predicting survival based on treating PSA-only relapse. Urol Oncol 2003; 21:292–304.

    Article  PubMed  Google Scholar 

  3. Powell SR. The antioxidant properties of zinc. J Nutr 2000; 130:1447–1454.

    Google Scholar 

  4. Truong-Tran AQ, Carter J, Ruffin RE, et al. The role of zinc in caspase activation and apoptotic cell death. Biometals 2001; 14:315–330.

    Article  PubMed  CAS  Google Scholar 

  5. Costello LC, Franklin RB. Novel role of zinc in the regulation of prostate citrate metabolism and its implications in prostate cancer. Prostate 1998; 35:285–296.

    Article  PubMed  CAS  Google Scholar 

  6. Pabon M, Lonnerdal, B. Effect of citrate on zinc bioavailability from milk, milk fractions and infant formulas. Nutr Res 1992; 13:103–111.

    Article  Google Scholar 

  7. Provinciali M, Stefano GD, Fabris N. Dose-dependent opposite effect of zinc on apoptosis in mouse thymocytes. Int J Immunopharmcol 1995; 17:735–744.

    Article  CAS  Google Scholar 

  8. Schrantz N, Auffredou MT, Bourgeade MF, et al. Zinc-mediated regulation of caspase activity: dose-dependent inhibition or activation of caspase-3 in the human Burkitt lymphoma B cells (Ramos). Cell Death Differ 2001; 8:152–161.

    Article  PubMed  CAS  Google Scholar 

  9. Costello LC, Liu Y, Franklin RB, et al. Zinc inhibition of mitochondrial aconitase and its importance in citrate metabolism of prostate epithelial cells. J Biol Chem 1997; 272:28875–28881.

    Article  PubMed  CAS  Google Scholar 

  10. Costello LC, Franklin RB, Narayan P. Citrate in the diagnosis of prostate cancer. Prostate 1999; 38:237–245.

    Article  PubMed  CAS  Google Scholar 

  11. Whelan P, Walker BE, Kelleher J. Zinc, vitamin A, and prostate cancer. Br J Urol 1983; 55:525–528.

    Article  PubMed  CAS  Google Scholar 

  12. Mocchegiani E, Muzzioli M, Giacconi R. Zinc, metallothioneins, immune responses, survival and ageing. Biogerontology 2000; 1:133–143.

    Article  PubMed  CAS  Google Scholar 

  13. Franklin RB, Ma J, Zou J, et al. Human ZIP1 is a major zinc uptake transpoter for the accumulation of zinc in prostate cells. J Inorg Biochem 2003; 96:435–442.

    Article  PubMed  CAS  Google Scholar 

  14. el-Deiry WS, Tokino T, Velculescu VE, et al. WAF1, a potential mediator of p53 tumor suppression. Cell 1993; 19:817–825.

    Article  Google Scholar 

  15. **ong Y, Hannon GJ, Zhang H, et al. p21 is a universal inhibitor of cyclin kinases. Nature 1993; 16:701–704

    Article  Google Scholar 

  16. Kluck RM, Bossy-Wetzel E, Green DR, et al. The release of cytochrome c from mitochondria: a primary site for Bcl-2 regulation of apoptosis. Science 1997; 275:1132–1136.

    Article  PubMed  CAS  Google Scholar 

  17. St Clair EG, Anderson SJ, Oltvai ZN. Bcl-2 counters apoptosis by Bax heterodimerization-dependent and -independent mechanisms in the T-cell lineage. J Biol Chem 1997; 272:29347–29355.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Urology, College of Medicine, the Catholic University of Korea, Seoul, 137701, Korea

    Sung Hoo Hong, Yong Sun Choi, Hyuk ** Cho, Ji Youl Lee, Joon Chul Kim, Tae Kon Hwang & Sae Woong Kim

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  1. Sung Hoo Hong
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  2. Yong Sun Choi
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  3. Hyuk ** Cho
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  4. Ji Youl Lee
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  5. Joon Chul Kim
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  6. Tae Kon Hwang
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  7. Sae Woong Kim
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Corresponding author

Correspondence to Sae Woong Kim.

Additional information

This study was supported by the National Research & Development Program for Cancer Control, Ministry for Health and Welfare, Republic of Korea (No. 1020080) and the Catholic Medical Center Research Foundation 2010.

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Hong, S.H., Choi, Y.S., Cho, H.J. et al. Antiproliferative effects of zinc-citrate compound on hormone refractory prostate cancer. Chin. J. Cancer Res. 24, 124–129 (2012). https://doi.org/10.1007/s11670-012-0124-9

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  • DOI: https://doi.org/10.1007/s11670-012-0124-9

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