Valproic Acid Alters Angiogenic and Trophic Gene Expression in Human Prostate Cancer Models

Anticancer Res. 2016 Oct;36(10):5079-5086. doi: 10.21873/anticanres.11077.

Abstract

Background/aim: Only a minority of men succumb to prostate cancer (PCa). Therapy to prevent progression would change treatment paradigms. We investigated the effect of valproic acid (VPA) on PCa cell proliferation and the effects on both angiogenesis and PCa-specific signaling.

Materials and methods: LNCaP cells were treated with VPA for 72 h and proliferation was measured. Cellular RNA extracts were used to measure gene expression with RT-profiler2 arrays. Genes with alterations were validated using real-time polymerase chain reaction and western blot.

Results: VPA led to a dose-dependent decrease in proliferation. Expression array data revealed an impact on modulators of angiogenesis. Additionally, several cell-cycle control transcripts were affected. There was a strong correlation between gene and protein expression levels for validated targets.

Conclusion: VPA decreases cellular proliferation of PCa cells in vitro and also affects gene expression suggestive of anti-angiogenic effect with a concomitant decrease in proliferation-related genes.

Keywords: Prostatic neoplasms; histone deacetylase inhibitors; neovascularization; pathologic; thrombospondin 1; valproic acid.

MeSH terms

  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Proliferation / genetics
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Humans
  • Male
  • Neovascularization, Pathologic / genetics
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / pathology
  • Valproic Acid / pharmacology*

Substances

  • Valproic Acid