Skip to main content
Log in

5,8,11,14-Eicosatetraynoic acid-induced destruction of mitochondria in human prostate cells (PC-3)

  • Regular Papers
  • Published:
In Vitro Cellular & Developmental Biology - Animal Aims and scope Submit manuscript

Summary

Culturing human prostate PC-3 cells for 4, 24, or 72 h in the presence of 5,8,11,14-eicosatetraynoic acid (ETYA), an inhibitor of arachidonic acid metabolism and cholesterol biosynthesis, markedly altered the morphology and reduced the number of mitochondria in the treated cells. Using quantitative electron microscopic morphometry, we documented changes in the number, form, area, matrix density, and integrity of the cristae and limiting membranes of mitochondria in cells cultured with ETYA. The inhibition of cholesterol synthesis or the substitution of ETYA for polyunsaturated fatty acids in the inner membrane may participate in the disruption of the mitochondria, which resembles the morphologic sequelae of oxidative stress. If sufficiently extensive, these changes could contribute to the inhibition of cellular proliferation by ETYA.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Anderson, K. M.; Ondrey, F.; Harris, J. E. Induction of monocyte like but not of macrophage morphology in U937 cells cultured with 5,8,11,10-eicosatetraynoic acid, a competitive inhibitor of arachidonic acid metabolism. Ann. Clin. Lab. Sci. 10:92–100; 1988.

    Google Scholar 

  2. Anderson, K. M.; Seed, T. M.; Ondrey, F., et al. Tumor mitochondrial matrix/cristae complexes as potential sites for anticancer therapy with polyunsaturated fatty acid analogs. Prostaglandins Leukotriens 40:137–141; 1990.

    Article  CAS  Google Scholar 

  3. Anderson, K. M.; Wygodny, J. B.; Ondrey, F., et al. Human PC-3 prostate cell line DNA synthesis is suppressed by eicosatetraynoic acid, an in vitro inhibitor of arachidonic acid metabolism. Prostate 12:3–12; 1988.

    Article  PubMed  CAS  Google Scholar 

  4. Begin, M. E.; Ells, G.; Horrobin, D. F. Polyunsaturated fatty acid induced cytotoxicity against tumor cells and its relationship to lipid peroxidation. JNCI 80:188–193; 1987.

    Article  Google Scholar 

  5. Cerutti, P. A. Proxidant states and tumor promotion. Science 227:375–381; 1985.

    Article  PubMed  CAS  Google Scholar 

  6. Ghadially, F. N. Mitochondria. In: Ultrastructural pathology of the cell and matrix. London: Butterworth; 1982:149–263.

    Google Scholar 

  7. Harris, J. E.; Anderson, K. M.; Ondrey, F., et al. Evidence of oxidative stress of ETYA (5,8,11,14-eicosatetraynoic acid) treated replication-arrested human prostate (PC-3) cells and its absence in replication-arrested human U937 monoblastoid cells. Proc. Am. Assoc. Cancer Res. 30:203; 1989.

    Google Scholar 

  8. Kaighn, M. E.; Narayan, K. S.; Ohnuki, Y., et al. Establishment and characterization of a human prostatic cell line (PC-3). Invest. Urol. 17:16–23; 1979.

    PubMed  CAS  Google Scholar 

  9. Kelly, J. P.; Johnson, M. C.; Parker, C. W. Effect on inhibition of arachidonic acid metabolism on mitogenesis in human lymphocytes. A possible role of thromboxanes and products of the lipoxygenase pathway. J. Immunol. 122:1563–1571; 1979.

    PubMed  CAS  Google Scholar 

  10. Kikugawa, K. Involvement of lipid oxidation products in the formation of lipofuscin. In: Nagy, I. Z. S., ed. Lipofuscin — 1987: State of the art. Amsterdam: Exerpta Medica; 1988:51–68.

    Google Scholar 

  11. Larsson, O.; Barrios, C.; Latham, C., et al. Abolition of mevinolin induced growth inhibition in human fibroblasts following transformation by simiam virus 40. Cancer Res. 49:5605–5610; 1989.

    PubMed  CAS  Google Scholar 

  12. Lawrence, H. J.; Suyelia, L. A.; Hack, F. M. Differential sensitivity of human myeloid leukemic cells to the antiproliferative effects of 5′-lipoxygenase inhibitors. Blood 68:145a, 458; 1986.

    Google Scholar 

  13. Masotti, L.; Casali, E.; Galeotti, T. Lipid peroxidation in tumor cells. Free Rad. Biol. Med. 4:377–386; 1988.

    Article  PubMed  CAS  Google Scholar 

  14. Nachbaur, J.; Colebeau, A.; Vignais, P. M. Distribution of membrane confined phospholipase A in rat hepatocytes. Biochim. Biophys. Acta. 274:426–446; 1972.

    Article  PubMed  CAS  Google Scholar 

  15. Ondrey, F.; Anderson, K. M.; Hoeltgen, D., et al. Differentiation of U937 cells induced by 5,8,11,14-eicosatetraynoic acid, a competitive inhibitor of arachidonic acid metabolism. Exp. Cell. Res. 1979:477–487; 1988.

    Article  Google Scholar 

  16. Ondrey, F.; Harris, J. E.; Anderson, K. M. Inhibition of U937 cells by eicosatetraynoic acid, a competitive inhibitor of arachidonic acid metabolism and its partial reversal by LTC4. Cancer Res. 49:1138–1142; 1989.

    PubMed  CAS  Google Scholar 

  17. Peterson, P. L. Tumor mitochondria and the bioenergetics of cancer cells. Prog. Exp. Tumor Res. 22:190–274; 1978.

    Google Scholar 

  18. Peterson, D. A.; Mehta, N.; Butterfield, J., et al. Polyunsaturated fatty acids stimulate superoxide formation in tumor cells: a mechanism for specific cytotoxicity and a model for tumor necrosis factor. Biochim. Biophys. Res. Commun. 155:1033–1037; 1988.

    Article  CAS  Google Scholar 

  19. Seed, T. M.; Rubenstein, M.; Anderson, K. M. Effects of castration and replacement of androgens on retrovirus expression in rat ventral prostate epithelial cells. Proc. Soc. Exp. Biol. Med. 169:470–479; 1980.

    Google Scholar 

  20. Taylor, A. S.; Morrison, A. R.; Russel, J. H. Incorporation of 5,8,11,14-eicosatetraynoic acid (ETYA) into cell lipids. Competitors with arachidonic acid for esterification. Prostaglandins 29:449–458; 1985.

    Article  PubMed  CAS  Google Scholar 

  21. Tobias, L. D.; Hamilton, J. G. The effect of 5,8,11,14-eicosatetraynoic acid on lipid metabolism. Lipids 14:181–193; 1979.

    Article  PubMed  CAS  Google Scholar 

  22. White, H. B. Normal and neoplastic brain tissue: phospholipid fatty acid and unsaturation number modifications in tumors. In: Wood, R., ed. Tumor lipids: biochemistry and metabolism. Champaign, IL: American Oil Chemists Society Press; 1973:75–88.

    Google Scholar 

  23. Wilson, D. E.; Anderson, K. M.; Seed, T. M., et al. Ultrastructural changes in human glioblastoma cells cultured with inhibitors of eicosanoid metabolism. Proc. Am. Assoc. Cancer Res. 31:81a, 480; 1990.

  24. Wilson, D. E.; Anderson, K. M.; Seed, T. Ultrastructural changes in human glioblastoma cells cultured with NDGA or ETYA, inhibitors of eicosanoid metabolism. Neurosurgery 27:523–531; 1990.

    Article  PubMed  CAS  Google Scholar 

  25. Wilson, D. E.; Ondrey, F.; Anderson, K. M., et al. ETYA and NDGA inhibit glioma cell division. Neurosurgery 71:551–557; 1989.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Anderson, K.M., Seed, T.M., Wilson, D.E. et al. 5,8,11,14-Eicosatetraynoic acid-induced destruction of mitochondria in human prostate cells (PC-3). In Vitro Cell Dev Biol - Animal 28, 410–414 (1992). https://doi.org/10.1007/BF02634044

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02634044

Key words

Navigation