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Evaluation of Vitamin D Analogs as Therapeutic Agents for Prostate Cancer

  • Conference paper
Vitamin D Analogs in Cancer Prevention and Therapy

Part of the book series: Recent Results in Cancer Research ((RECENTCANCER,volume 164))

Abstract

Prostate cancer cells contain specific receptors (VDR) for 1α,25-dihydroxyvitamin D (1α,(OH)2D3), which is known to inhibit the proliferation and invasiveness of these cells. These findings support the use of 1α,(OH)2D3for prostate cancer therapy. However, because 1α,(OH)2D3can cause hypercalcemia, analogs of 1α,(OH)2D3that are less calcemic but which exhibit potent antiproliferative activity would be attractive as therapeutic agents. We studied four vitamin D compounds: 25-hydroxyvitaminD3 [25(OH)D3], which is converted to 1α,(OH)2D33 in prostate cells, and three analogs of 1α,(OH)2D33: EB1089, 19- nor-1α,(OH)2D32 and hexafluoro-1α,(OH)2D33 (F6-1α,(OH)2D33). 19-nor- 1α,(OH)2D32 has been shown to be less calcemic than 1α,(OH)2D33 in clinical trials. F6-1α,(OH)2D33 has been shown to be 100-fold more active than 1α,(OH)2D33 and to be longer-lasting in inhibiting keratinocyte proliferation in vitro. EB1089 has been shown to be less calcemic than 1α,(OH)2D33 in rats implanted with Leydig cell tumors. For 25(OH)D3, 19-nor-1α,(OH)2D32 and F6-1α,(OH)2D33, we studied the in vitro effects and compared their activity to 1α,(OH)2D33 on cellular proliferation by 3H-thymidine incorporation assay. In addition, we studied transactivation of the VDR in the presence of 25(OH)D3 and 19-nor-1α,(OH)2D32 in prostate cells. For EB1089, we compared its inhibition of prostate cancer metastasis to that induced by 1α,(OH)2D33 in vivo in the rat Dunning MAT LyLu prostate cancer model. We found that 1α,(OH)2D33 and 19-nor-1α,(OH)2D32 caused similar dose-dependent inhibition in 3H-thymidine incorporation into DNA in prostate cells and behaved similarly in the CAT reporter gene transactivation assay in PC-3/VDR cells.

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Authors and Affiliations

  1. Department of Medicine, Endocrine Section, Boston University School of Medicine, 715 Albany Street, Boston, MA, 02118, USA

    Tai C. Chen

Authors
  1. Tai C. Chen
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  2. Michael F. Holick
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  3. Bal L. Lokeshwar
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  4. Kerry L. Burnstein
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  5. Gary G. Schwartz
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Editors and Affiliations

  1. Hautklinik und Poliklinik der Universitätskliniken des Saarlandes, Kirrberger Str., 66421, Homburg/Saar

    Jörg Reichrath  & Wolfgang Tilgen  & 

  2. Frauenklinik des Universitätsklinikums der Eberhard-Karls-Universität, Calwerstr. 7, 71076, Tübingen

    Michael Friedrich

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© 2003 Springer-Verlag Berlin Heidelberg

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Chen, T.C., Holick, M.F., Lokeshwar, B.L., Burnstein, K.L., Schwartz, G.G. (2003). Evaluation of Vitamin D Analogs as Therapeutic Agents for Prostate Cancer. In: Reichrath, J., Tilgen, W., Friedrich, M. (eds) Vitamin D Analogs in Cancer Prevention and Therapy. Recent Results in Cancer Research, vol 164. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-55580-0_20

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  • DOI: https://doi.org/10.1007/978-3-642-55580-0_20

  • Publisher Name: Springer, Berlin, Heidelberg

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