Cancer Cell Biology

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Role of 24-hydroxylase in vitamin D3 growth response of OVCAR-3 ovarian cancer cells

  1. Susanna Miettinen1,†,*,
  2. Merja H. Ahonen2,
  3. Yan-Ru Lou2,
  4. Tommi Manninen1,
  5. Pentti Tuohimaa2,
  6. Heimo Syvälä1,
  7. Timo Ylikomi1,3

Article first published online: 21 OCT 2003

DOI: 10.1002/ijc.11520

Issue

International Journal of Cancer

International Journal of Cancer

Volume 108, Issue 3, pages 367–373, 20 January 2004

Additional Information

How to Cite

Miettinen, S., Ahonen, M. H., Lou, Y.-R., Manninen, T., Tuohimaa, P., Syvälä, H. and Ylikomi, T. (2004), Role of 24-hydroxylase in vitamin D3 growth response of OVCAR-3 ovarian cancer cells. Int. J. Cancer, 108: 367–373. doi: 10.1002/ijc.11520

Author Information

  1. 1

    Department of Cell Biology, Medical School, University of Tampere, Tampere, Finland

  2. 2

    Department of Anatomy, Medical School, University of Tampere, Tampere, Finland

  3. 3

    Department of Clinical Chemistry, Tampere University Hospital, Tampere, Finland

  1. †

    Fax: +358-3-2156170

*Department of Cell Biology, Medical School, University of Tampere, FIN-33014 University of Tampere, Finland

Publication History

  1. Issue published online: 21 NOV 2003
  2. Article first published online: 21 OCT 2003
  3. Manuscript Accepted: 5 AUG 2003
  4. Manuscript Revised: 25 JUN 2003
  5. Manuscript Received: 20 FEB 2003

Funded by

  • Medical Research Fund of Tampere University Hospital
  • Finnish Cancer Society

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Keywords:

  • vitamin D;
  • EB 1089;
  • 1α-hydroxylase;
  • 24-hydroxylase;
  • ovary;
  • cell growth

Abstract

Vitamin D and its analogues are potent regulators of cell growth and differentiation both in vivo and in vitro. We studied the effects of 25-hydroxyvitamin D3 [25(OH)D3], 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] and vitamin D analogue, EB 1089, on the growth of a human ovarian cancer cell line, OVCAR-3. We also studied the expression of vitamin D metabolising enzymes 24-hydroxylase (24OHase) and 1α-hydroxylase (1αOHase). Our results showed that high concentrations (10 and 100 nM) of 1,25(OH)2D3 inhibited a cell proliferation, whereas low concentration (0.1 nM) stimulated growth of the OVCAR-3 cells. In the concentration range of 10–500 nM a prohormone, 25(OH)D3, stimulated growth. An amount of 1 nM EB 1089 and 100 nM 1,25(OH)2D3 inhibited growth with an equal magnitude. The expression of 24OHase was strongly induced by 1,25(OH)2D3 and EB 1089 in OVCAR-3 cells, and analysis of vitamin D metabolites showed the functionality of 24OHase. An inhibition of 24OHase activity with a novel 24OHase inhibitor enhanced growth-inhibiting effects of 1,25(OH)2D3 and suppressed the growth stimulation of 100 nM 25(OH)D3. We also report the expression of a vitamin D activating enzyme, 1αOHase, in 7 ovarian cancer cell lines. The production of 1,25(OH)2D3 in OVCAR-3 cells was low, possibly due to an extensive activity of 24OHase or a low 1αOHase activity. These results suggest that in ovarian cancer cells vitamin D metabolizing enzymes might play a key role in modulating the growth response to vitamin D. The possible mitogenic effects of vitamin D should be considered when evaluating treatment of ovarian cancer with vitamin D. © 2003 Wiley-Liss, Inc.

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