Theaflavins retard human breast cancer cell migration by inhibiting NF-kappaB via p53-ROS cross-talk

FEBS Lett. 2010 Jan 4;584(1):7-14. doi: 10.1016/j.febslet.2009.10.081.

Abstract

The present study demonstrates that theaflavins exploit p53 to impede metastasis in human breast cancer cells. Our data suggest that p53-dependent reactive oxygen species (ROS) induce p53-phosphorylation via p38MAPK in a feedback loop to inhibit IkappaBalpha-phosphorylation and NF-kappaB/p65 nuclear translocation, thereby down-regulating the metastatic proteins metalloproteinase (MMP)-2 and MMP-9. When wild-type p53-expressing MCF-7 cells are transfected with p53 short-interfering RNA, or treated with a pharmacological inhibitor of ROS, theaflavins fail to inhibit NF-kappaB-mediated cell migration. On the other hand, NF-kappaB over-expression bestows MCF-7 cells with resistance to the anti-migratory effect of theaflavins. These results indicate that inhibition of NF-kappaB via p53-ROS crosstalk is a pre-requisite for theaflavins to accomplish the anti-migratory effect in breast cancer cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus / drug effects
  • Antioxidants / pharmacology*
  • Biflavonoids / pharmacology*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology*
  • Carcinoma / metabolism
  • Carcinoma / secondary*
  • Catechin / pharmacology*
  • Cell Line, Tumor
  • Cell Movement / drug effects*
  • Cell Nucleus / metabolism
  • Female
  • Humans
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / metabolism
  • Matrix Metalloproteinase Inhibitors
  • NF-kappa B / antagonists & inhibitors*
  • NF-kappa B / metabolism
  • Neoplasm Metastasis
  • Reactive Oxygen Species / metabolism
  • Tumor Suppressor Protein p53 / antagonists & inhibitors*
  • Tumor Suppressor Protein p53 / metabolism
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Antioxidants
  • Biflavonoids
  • Matrix Metalloproteinase Inhibitors
  • NF-kappa B
  • Reactive Oxygen Species
  • Tumor Suppressor Protein p53
  • theaflavin
  • Catechin
  • p38 Mitogen-Activated Protein Kinases
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9