DADS downregulates the Rac1-ROCK1/PAK1-LIMK1-ADF/cofilin signaling pathway, inhibiting cell migration and invasion

Oncol Rep. 2013 Feb;29(2):605-12. doi: 10.3892/or.2012.2168. Epub 2012 Dec 6.

Abstract

The aim of this study was to explore the molecular mechanisms of the diallyl disulfide (DADS)-mediated downregulation of LIM kinase-1 (LIMK1) and the consequent inhibition of the migration and invasion of human colorectal cancer cells. RNA interference technology was used to establish stable LIMK1-miRNA/SW480 cell lines. The effects of DADS and LIMK1 RNA interference on the migration and invasion of SW480 cells were observed by scratch wound healing assay and Transwell migration assay. The effects of DADS on signaling molecules of the Rac1-Rho kinase (ROCK)1/p21-activated kinase (PAK)1-LIM kinase (LIMK)1-actin depolymerizing factor (ADF)/cofilin pathway in SW480 cells were examined by RT-PCR and western blot analysis. The healing and migration rate of the SW480 cells was significantly reduced and the cell penetrating ability was significantly suppressed (P<0.05) following treatment with DADS (45 mg/l). The immunohistochemistry and western blot analysis results showed that DADS significantly downregulated LIMK1 protein expression and suppressed LIMK1 protein phosphorylation. Furthermore, the RT-PCR and western blot analysis results revealed that DADS suppressed Rac1, ROCK1, PAK1, LIMK1 and destrin mRNA and protein expression, as well as the protein phosphorylation of LIMK1 and cofilin 1. The data demonstrate that LIMK1 expression positively correlates with the SW480 cell migration and invasion ability. DADS downregulates the Rac1-ROCK1/PAK1-LIMK1-ADF/cofilin signaling pathway, suppressing SW480 cell migration and invasion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allyl Compounds / pharmacology*
  • Cell Line, Tumor
  • Cell Movement / drug effects*
  • Cofilin 1 / metabolism
  • Colorectal Neoplasms / metabolism*
  • Colorectal Neoplasms / pathology*
  • Destrin / metabolism
  • Disulfides / pharmacology*
  • Down-Regulation / drug effects
  • Gene Expression Regulation, Neoplastic
  • Gene Silencing
  • Humans
  • Lim Kinases / genetics
  • Lim Kinases / metabolism*
  • MicroRNAs
  • Neoplasm Invasiveness / genetics
  • RNA, Messenger / metabolism
  • Signal Transduction / drug effects*
  • p21-Activated Kinases / metabolism
  • rac1 GTP-Binding Protein / metabolism
  • rho-Associated Kinases / metabolism

Substances

  • Allyl Compounds
  • Cofilin 1
  • DSTN protein, human
  • Destrin
  • Disulfides
  • MicroRNAs
  • RAC1 protein, human
  • RNA, Messenger
  • diallyl disulfide
  • LIMK1 protein, human
  • Lim Kinases
  • PAK1 protein, human
  • ROCK1 protein, human
  • p21-Activated Kinases
  • rho-Associated Kinases
  • rac1 GTP-Binding Protein