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Inhibition of prostate cancer growth by vitamin D: Regulation of target gene expression

Aruna V Krishnan1, Donna M Peehl, David Feldman

  • 1Department of Medicine, Stanford University School of Medicine, Stanford, California 94305, USA.

Journal of Cellular Biochemistry
|January 10, 2003
PubMed

Insights

Vitamin D (1,25(OH)(2)D(3)) inhibits prostate cancer (PCa) cell growth by arresting the cell cycle. Clinical trials show it can slow prostate-specific antigen rise, indicating therapeutic potential for PCa.

Area of Science:

  • Endocrinology
  • Oncology
  • Molecular Biology

Background:

  • Prostate cancer (PCa) cells express vitamin D receptors (VDR).
  • 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) inhibits the growth of normal, benign, and cancerous prostate epithelial cells.
  • Enzymes 25-hydroxyvitamin D(3) 24-hydroxylase and 25-hydroxyvitamin D(3) 1alpha-hydroxylase modulate 1,25(OH)(2)D(3) activity.

Purpose of the Study:

  • To investigate the antiproliferative effects of 1,25(OH)(2)D(3) in prostate cancer cells.
  • To identify target genes regulated by 1,25(OH)(2)D(3) in prostate cancer.
  • To explore the therapeutic potential of 1,25(OH)(2)D(3) in prostate cancer patients.

Main Methods:

  • Cell culture experiments with LNCaP human PCa cells.
  • cDNA microarray analyses of prostatic epithelial and PCa cells.
  • A small clinical trial in PCa patients measuring prostate-specific antigen (PSA) levels.

Main Results:

  • 1,25(OH)(2)D(3) induces cell cycle arrest in PCa cells, primarily through IGFBP-3 and p21.
  • Microarray analysis revealed numerous 1,25(OH)(2)D(3)-regulated genes involved in growth, oxidative stress, and cell interactions.
  • A clinical trial demonstrated that 1,25(OH)(2)D(3) can slow the rate of PSA rise in PCa patients.

Conclusions:

  • 1,25(OH)(2)D(3) exhibits antiproliferative activity in prostate cancer via cell cycle arrest and regulation of multiple target genes.
  • These findings support the therapeutic potential of calcitriol and its analogs for prostate cancer treatment and chemoprevention.
  • Further research is warranted to fully elucidate the role of vitamin D in managing prostate cancer.

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