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Vitamin D Analogs in Cancer Prevention and Therapy pp 205–221Cite as

The Role of Vitamin D in Prostate Cancer

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

Abstract

Prostate cancer (PCa) cells harbor receptors for vitamin D (VDR) as well as androgens (AR). 1,25-dihydroxyvitamin D3[1,(OH)2D3] increases AR expression and enhances androgen actions linking the two receptor systems.1,(OH)2D3exhibits antiproliferative activity in both AR-positive and AR-negative PCa cells. Less calcemic analogs of 1,(OH)2D3, with more antiproliferative activity, are being developed and will be more useful clinically. The mechanisms underlying differential analog activity are being investigated. In target cells, 1,(OH)2D3induces 24-hydroxylase, the enzyme that catalyzes its selfinactivation.Co-treatment with 24-hydroxylase inhibitors enhances the antiproliferative activity of calcitriol. Primary cultures of normal or cancer-derived prostatic epithelial cells express 1a-hydroxylase, the enzyme that catalyzes the synthesis of 1,(OH)2D3, the levels being much lower in the cancerderived cells and in PCa cell lines. This finding raises the possibility of using 25-hydroxyvitamin D3[25(OH)D3] as a chemopreventive agent in PCa.In LNCaP human PCa cells, 1,(OH)2D3and its analogs exert antiproliferative activity predominantly by cell cycle arrest, but also induce apoptosis, although to a much lesser degree. Growth arrest is mediated by induction of IGF binding protein-3 (IGFBP-3), which in turn increases the expression of the cell cycle inhibitor p21, leading to growth arrest. Other actions of 1,(OH)2D3in PCa cells include promotion of pro-differentiation effects and inhibition of tumor cell invasion,metastasis and angiogenesis.

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Authors and Affiliations

  1. Department of Medicine, Division of Endocrinology, Stanford University School of Medicine, Stanford, CA, 94305-5103, USA

    David Feldman

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  1. Aruna V. Krishnan
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  2. Donna M. Peehl
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  3. David Feldman
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  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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Krishnan, A.V., Peehl, D.M., Feldman, D. (2003). The Role of Vitamin D in 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_15

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  • DOI: https://doi.org/10.1007/978-3-642-55580-0_15

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-62435-3

  • Online ISBN: 978-3-642-55580-0

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