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

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.

• Authors: Avani R Vyas, Shivendra V Singh
• Journal: European journal of nutrition (Eur J Nutr) Vol. 53 Issue 3 Pg. 843-52 (Apr 2014) ISSN: 1436-6215 [Electronic] Germany
• PMID: 24092501 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

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

Topics

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