Caffeine inhibits migration in glioma cells through the ROCK-FAK pathway

Cell Physiol Biochem. 2014;33(6):1888-98. doi: 10.1159/000362966.


Aims: Glioma is the most malignant brain tumor that has the ability to migrate and invade the CNS. In this study, we investigated the signaling mechanism of caffeine on the migration of glioma cells.

Methods: The effect of caffeine on cell migration was evaluated using Transwell and wound healing assays. The expression of the focal adhesion complex as it related to cell migration was assayed using Western blotting and immunostaining.

Results: Caffeine decreased the migration of rat C6 and human U87MG glioma cells and down-regulated the expression of phosphorylated focal adhesion kinase (p-FAK) and p-paxillin. Caffeine also decreased p-FAK staining at the edge of glioma cells and disassembled actin stress fibers. Additionally, caffeine elevated expression of phosphorylated myosin light chain (p-MLC), an effect that could be blocked by Y27632, a rho-associated protein kinase (ROCK) inhibitor, but not myosin light chain kinase inhibitor, ML-7. Y27632 also inhibited the caffeine-reduced expression of p-FAK and p-paxillin as well as cell migration.

Conclusion: Caffeine decreased the migration of glioma cell through the ROCK-focal adhesion complex pathway; this mechanism may be useful as part of clinical therapy in the future.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amides / pharmacology
  • Animals
  • Blotting, Western
  • Caffeine / pharmacology*
  • Cell Adhesion / drug effects
  • Cell Line, Tumor
  • Cell Movement / drug effects*
  • Cell Survival / drug effects
  • Central Nervous System Stimulants / pharmacology
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / pharmacology
  • Focal Adhesion Protein-Tyrosine Kinases / metabolism*
  • Glioma / metabolism
  • Glioma / pathology
  • Humans
  • Microscopy, Fluorescence
  • Myosin Light Chains / metabolism
  • Paxillin / metabolism
  • Phosphorylation / drug effects
  • Pyridines / pharmacology
  • Rats
  • Signal Transduction / drug effects*
  • Time Factors
  • rho-Associated Kinases / antagonists & inhibitors
  • rho-Associated Kinases / metabolism*


  • Amides
  • Central Nervous System Stimulants
  • Enzyme Inhibitors
  • Myosin Light Chains
  • Paxillin
  • Pyridines
  • Y 27632
  • Caffeine
  • Focal Adhesion Protein-Tyrosine Kinases
  • rho-Associated Kinases