Aloe emodin inhibits colon cancer cell migration/angiogenesis by downregulating MMP-2/9, RhoB and VEGF via reduced DNA binding activity of NF-κB

Eur J Pharm Sci. 2012 Apr 11;45(5):581-91. doi: 10.1016/j.ejps.2011.12.012. Epub 2011 Dec 30.

Abstract

Aloe emodin (AE), a natural anthraquinone, is reported to have antiproliferative activity in various cancer cell lines. In this study we analyzed molecular mechanisms involved in the antimigratory and antiangiogenic activity of this hydroxy anthraquinone in colon cancer cell, WiDr. Our results show that a relatively non toxic concentration of AE suppressed the phorbol-12-myristyl-13-acetate (PMA) induced migration and invasion of tumor cells. On analysis for the molecules involved in the migration/invasion, we found AE downregulated mRNA expression and promoter/gelatinolytic activity of Matrix Metalloproteinase (MMP)-2/9, as well as the RhoB expression at gene and protein level. It was also a strong inhibitor of Vascular Endothelial Growth Factor (VEGF) expression, promoter activity and endothelial cell migration/invasion and in vitro angiogenesis. AE suppressed the nuclear translocation and DNA binding of NF-κB, which is an important transcription factor for controlling MMP-2/9 and VEGF gene expression. Taken together these data indicate that AE target multiple molecules responsible for cellular invasion, migration and angiogenesis. Inhibitory effect on angiogenic and metastatic regulatory processes make AE a sensible candidate as a specific blocker of tumor associated events.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inhibitors / pharmacology
  • Anthraquinones / pharmacology*
  • Cell Movement / drug effects*
  • Cell Movement / genetics
  • Cell Nucleus / drug effects
  • Cell Nucleus / metabolism
  • Colonic Neoplasms / drug therapy*
  • Colonic Neoplasms / genetics
  • Colonic Neoplasms / metabolism
  • Colonic Neoplasms / pathology
  • DNA / genetics
  • DNA / metabolism
  • Down-Regulation / drug effects
  • Endothelial Cells / drug effects
  • Endothelial Cells / metabolism
  • Endothelial Cells / pathology
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MAP Kinase Signaling System / drug effects
  • Matrix Metalloproteinase 2 / genetics
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / genetics
  • Matrix Metalloproteinase 9 / metabolism
  • Matrix Metalloproteinase Inhibitors*
  • NF-kappa B / antagonists & inhibitors
  • NF-kappa B / genetics
  • NF-kappa B / metabolism
  • Neoplasm Invasiveness
  • Neovascularization, Pathologic / drug therapy
  • Neovascularization, Pathologic / genetics
  • Neovascularization, Pathologic / metabolism
  • Neovascularization, Pathologic / pathology
  • Phosphorylation / drug effects
  • Promoter Regions, Genetic
  • Protein Transport / drug effects
  • RNA, Messenger / genetics
  • Signal Transduction / drug effects
  • Tumor Cells, Cultured
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors*
  • Vascular Endothelial Growth Factor A / genetics
  • rhoB GTP-Binding Protein / antagonists & inhibitors*
  • rhoB GTP-Binding Protein / genetics
  • rhoB GTP-Binding Protein / metabolism

Substances

  • Angiogenesis Inhibitors
  • Anthraquinones
  • Matrix Metalloproteinase Inhibitors
  • NF-kappa B
  • RNA, Messenger
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • DNA
  • aloe emodin
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9
  • rhoB GTP-Binding Protein