Vitamin C supplementation prevents testosterone-induced hyperplasia of rat prostate by down-regulating HIF-1alpha

J Nutr Biochem. 2010 Sep;21(9):801-8. doi: 10.1016/j.jnutbio.2009.06.004. Epub 2009 Aug 27.


Benign prostatic hyperplasia (BPH) is a disease that impairs the well-being of many aged men. To alleviate BPH symptoms or to find a cure for this disease, key molecules should be identified that control prostate cell proliferation. Recently, HIF-1alpha has attracted attention in this context, because it is highly expressed in hyperplasic prostates and prevents prostate cell death. Thus, given that vitamin C inhibits HIF-1alpha expression in several malignant tumors, we examined its therapeutic potential in BPH. HIF-1alpha was noticeably induced by testosterone in prostate cells, and this HIF-1alpha induction was abolished by vitamin C. Vascular endothelial growth factor (VEGF) promoter activity reporter assays and semi-quantitative RT-PCR revealed that vitamin C inhibited HIF-1-dependent VEGF expression. Furthermore, HIF-1alpha suppression by vitamin C was rescued by knocking down HIF-prolyl hydroxylase-2, suggesting that vitamin C destabilizes HIF-1alpha via prolyl hydroxylation. Moreover, vitamin C treatment abolished cell proliferation induced by testosterone treatment to the control level. These results suggest that vitamin C inhibits testosterone-induced HIF-1alpha expression and by so doing effectively prevents prostate hyperplasia. In male rats, testosterone treatment for 4 weeks induced prostate hyperplasia. Furthermore, HIF-1alpha and VEGF levels were significantly elevated in hyperplasic prostates. In vitamin C-treated rats, however, most prostate hyperplasia parameters and prostrate HIF-1alpha/VEGF levels were markedly reduced. Accordingly, our findings indicate that vitamin C could be further developed clinically for use as an anti-BPH agent.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Ascorbic Acid / pharmacology
  • Ascorbic Acid / therapeutic use*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Down-Regulation
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / antagonists & inhibitors
  • Hypoxia-Inducible Factor 1, alpha Subunit / biosynthesis*
  • Male
  • Prostate / drug effects
  • Prostate / metabolism
  • Prostatic Hyperplasia / drug therapy*
  • Prostatic Hyperplasia / prevention & control
  • Rats
  • Rats, Sprague-Dawley
  • Testosterone / antagonists & inhibitors
  • Testosterone / pharmacology
  • Vascular Endothelial Growth Factor A / biosynthesis


  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Vascular Endothelial Growth Factor A
  • Testosterone
  • Ascorbic Acid