The anandamide analog, Met-F-AEA, controls human breast cancer cell migration via the RHOA/RHO kinase signaling pathway

Endocr Relat Cancer. 2008 Dec;15(4):965-74. doi: 10.1677/ERC-08-0030. Epub 2008 Aug 1.

Abstract

The endocannabinoid system regulates cell proliferation and migration in human breast cancer cells. In this study, we showed that a metabolically stable analog of anandamide, 2-methyl-2'-F-anandamide (Met-F-AEA), inhibited the RHOA activity and caused a RHOA delocalization from the cell membrane to cytosol determining a decrease in actin stress fibers. Overexpression of a dominant negative of RHOA activity and treatment of these cells with a RHO-associated protein kinase (ROCK) inhibitor, Y 27632, mimicked Met-F-AEA effects on actin organization and cell migration. We suggest that the inhibitory effect of Met-F-AEA on tumor cell migration could be related to RHOA-ROCK-dependent signaling pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Amides / pharmacology
  • Arachidonic Acids / pharmacology*
  • Blotting, Western
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology*
  • Cannabinoids / pharmacology
  • Cell Membrane / enzymology
  • Cell Movement / drug effects*
  • Cytoskeleton / metabolism
  • Cytosol / enzymology
  • Female
  • Fluorescent Antibody Technique
  • Humans
  • Mevalonic Acid / pharmacology
  • Neoplasm Invasiveness
  • Pyridines / pharmacology
  • Signal Transduction / drug effects*
  • rho-Associated Kinases / metabolism*
  • rhoA GTP-Binding Protein / metabolism*

Substances

  • 2-methylarachidonyl-2'-fluoroethylamide
  • Actins
  • Amides
  • Arachidonic Acids
  • Cannabinoids
  • Pyridines
  • Y 27632
  • rho-Associated Kinases
  • rhoA GTP-Binding Protein
  • Mevalonic Acid