Vitamin D in Prostate Cancer

Jungmi Ahn, Sulgi Park, Baltazar Zuniga, Alakesh Bera, Chung Seog Song, Bandana Chatterjee

Research output: Contribution to journalArticle

Abstract

Metastatic castration-resistant prostate cancer (mCRPC) is a progressive, noncurable disease induced by androgen receptor (AR) upon its activation by tumor tissue androgen, which is generated from adrenal steroid dehydroepiandrosterone (DHEA) through intracrine androgen biosynthesis. Inhibition of mCRPC and early-stage, androgen-dependent prostate cancer by calcitriol, the bioactive vitamin D3 metabolite, is amply documented in cell culture and animal studies. However, clinical trials of calcitriol or synthetic analogs are inconclusive, although encouraging results have recently emerged from pilot studies showing efficacy of a safe-dose vitamin D3 supplementation in reducing tumor tissue inflammation and progression of low-grade prostate cancer. Vitamin D-mediated inhibition of normal and malignant prostate cells is caused by diverse mechanisms including G1/S cell cycle arrest, apoptosis, prodifferentiation gene expression changes, and suppressed angiogenesis and cell migration. Biological effects of vitamin D are mediated by altered expression of a gene network regulated by the vitamin D receptor (VDR), which is a multidomain, ligand-inducible transcription factor similar to AR and other nuclear receptors. AR-VDR cross talk modulates androgen metabolism in prostate cancer cells. Androgen inhibits vitamin D-mediated induction of CYP24A1, the calcitriol-degrading enzyme, while vitamin D promotes androgen inactivation by inducing phase I monooxygenases (e.g., CYP3A4) and phase II transferases (e.g., SULT2B1b, a DHEA-sulfotransferase). CYP3A4 and SULT2B1b levels are markedly reduced and CYP24A1 is overexpressed in advanced prostate cancer. In future trials, combining low-calcemic, potent next-generation calcitriol analogs with CYP24A1 inhibition or androgen supplementation, or cancer stem cell suppression by a phytonutrient such as sulfarophane, may prove fruitful in prostate cancer prevention and treatment.

Original languageEnglish (US)
JournalVitamins and Hormones
DOIs
StateAccepted/In press - 2015
Externally publishedYes

Fingerprint

Vitamin D
Androgens
Prostatic Neoplasms
Calcitriol
Androgen Receptors
Cytochrome P-450 CYP3A
Calcitriol Receptors
Cholecalciferol
Castration
Receptor Cross-Talk
G1 Phase Cell Cycle Checkpoints
Dehydroepiandrosterone
Neoplastic Stem Cells
Gene Regulatory Networks
Phytochemicals
Cytoplasmic and Nuclear Receptors
Transferases
Mixed Function Oxygenases
Cell Movement
Prostate

Keywords

  • Androgen receptor
  • Growth inhibition VDR metabolism
  • Intracrine androgen metabolism
  • Metastatic castration-resistant prostate cancer
  • Transcriptional regulation
  • Vitamin D
  • Vitamin D receptor

ASJC Scopus subject areas

  • Endocrinology
  • Physiology

Cite this

Ahn, J., Park, S., Zuniga, B., Bera, A., Song, C. S., & Chatterjee, B. (Accepted/In press). Vitamin D in Prostate Cancer. Vitamins and Hormones. https://doi.org/10.1016/bs.vh.2015.10.012

Vitamin D in Prostate Cancer. / Ahn, Jungmi; Park, Sulgi; Zuniga, Baltazar; Bera, Alakesh; Song, Chung Seog; Chatterjee, Bandana.

In: Vitamins and Hormones, 2015.

Research output: Contribution to journalArticle

Ahn, J, Park, S, Zuniga, B, Bera, A, Song, CS & Chatterjee, B 2015, 'Vitamin D in Prostate Cancer', Vitamins and Hormones. https://doi.org/10.1016/bs.vh.2015.10.012
Ahn J, Park S, Zuniga B, Bera A, Song CS, Chatterjee B. Vitamin D in Prostate Cancer. Vitamins and Hormones. 2015. https://doi.org/10.1016/bs.vh.2015.10.012
Ahn, Jungmi ; Park, Sulgi ; Zuniga, Baltazar ; Bera, Alakesh ; Song, Chung Seog ; Chatterjee, Bandana. / Vitamin D in Prostate Cancer. In: Vitamins and Hormones. 2015.
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