5-Aminosalicylic acid inhibits TGF-beta1 signalling in colorectal cancer cells

Cancer Lett. 2010 Jan 1;287(1):82-90. doi: 10.1016/j.canlet.2009.05.033. Epub 2009 Jun 21.

Abstract

The transforming growth factor-beta (TGF-beta) pathway is an important pathway in the initiation and progression of colorectal cancer. We aimed to determine the effects of 5-aminosalicylic acid (5-ASA) on TGF-beta signalling in colorectal cancer cells in vitro. 5-ASA inhibited TGF-beta1 signalling in HCT116 cells and colonic fibroblasts, as judged by a TGF-beta-specific reporter gene assay, plasminogen activator inhibitor-1 mRNA and protein levels, fibroblast trans-differentiation, Smad3 phosphorylation and nuclear translocation. We conclude that 5-ASA inhibits TGF-beta1 signalling in colorectal cancer cells, and might be a potent adjuvant therapeutic drug, interfering with aberrant TGF-beta signalling in colorectal cancer.

MeSH terms

  • Active Transport, Cell Nucleus / drug effects
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Cell Line, Tumor
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / pathology
  • Humans
  • Mesalamine / pharmacology*
  • Phosphorylation
  • Signal Transduction / drug effects*
  • Smad3 Protein / metabolism
  • Transforming Growth Factor beta1 / antagonists & inhibitors*

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • SMAD3 protein, human
  • Smad3 Protein
  • Transforming Growth Factor beta1
  • Mesalamine