Functional relevance of D,L-sulforaphane-mediated induction of vimentin and plasminogen activator inhibitor-1 in human prostate cancer cells

Eur J Nutr. 2014 Apr;53(3):843-52. doi: 10.1007/s00394-013-0588-5. Epub 2013 Oct 4.

Abstract

Purpose: D,L-Sulforaphane (SFN) is a promising chemopreventive agent with in vivo efficacy against prostate cancer in experimental rodents. This study was undertaken to determine the role of vimentin and plasminogen activator inhibitor-1 (PAI-1) in anticancer effects of SFN.

Methods: Effect of SFN on levels of different proteins was determined by Western blotting or immunofluorescence microscopy. RNA interference of vimentin and PAI-1 was achieved by transient transfection. Apoptosis was quantified by flow cytometry. Transwell chambers were used to determine cell migration.

Results: Exposure of PC-3 and DU145 human prostate cancer cells to SFN resulted in induction of vimentin protein, which was accompanied by down-regulation of E-cadherin protein expression. The SFN-mediated induction of vimentin was also observed in a normal human prostate epithelial cell line. RNA interference of vimentin did not have any appreciable effect on early or late apoptosis resulting from SFN exposure. On the other hand, SFN-mediated inhibition of PC-3 and DU145 cell migration was significantly augmented by knockdown of the vimentin protein. Knockdown of vimentin itself was inhibitory against cell migration. The SFN-treated cells also exhibited induction of PAI-1, which is an endogenous inhibitor of urokinase-type plasminogen activator system. Similar to vimentin, PAI-1 knockdown resulted in a modest augmentation of PC-3 cell migration inhibition by SFN. Tumors from SFN-treated transgenic adenocarcinoma of mouse prostate mice showed a 1.7-fold increase in vimentin protein level compared with control tumors.

Conclusion: The present study indicates that vimentin and PAI-1 inductions confer modest protection against SFN-mediated inhibition of prostate cancer cell migration.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / prevention & control
  • Animals
  • Anticarcinogenic Agents / pharmacology*
  • Anticarcinogenic Agents / therapeutic use
  • Apoptosis / drug effects
  • Cadherins / antagonists & inhibitors
  • Cadherins / metabolism
  • Cell Line
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Down-Regulation / drug effects
  • Gene Knockdown Techniques
  • Humans
  • Isothiocyanates / pharmacology*
  • Isothiocyanates / therapeutic use
  • Male
  • Mice, Transgenic
  • Neoplasm Proteins / agonists
  • Neoplasm Proteins / antagonists & inhibitors
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism
  • Plasminogen Activator Inhibitor 1 / agonists*
  • Plasminogen Activator Inhibitor 1 / chemistry
  • Plasminogen Activator Inhibitor 1 / genetics
  • Plasminogen Activator Inhibitor 1 / metabolism
  • Prostate / drug effects
  • Prostate / metabolism
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / prevention & control
  • RNA Interference
  • Sulfoxides
  • Up-Regulation / drug effects*
  • Vimentin / agonists*
  • Vimentin / antagonists & inhibitors
  • Vimentin / genetics
  • Vimentin / metabolism

Substances

  • Anticarcinogenic Agents
  • Cadherins
  • Isothiocyanates
  • Neoplasm Proteins
  • Plasminogen Activator Inhibitor 1
  • SERPINE1 protein, human
  • Sulfoxides
  • Vimentin
  • sulforaphane