The anandamide analog, Met-F-AEA, controls human breast cancer cell migration via the RHOA/RHO kinase signaling pathway.
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.
Laezza
Chiara
C
Istituto di Endocrinologia e Oncologia Sperimentale, Consiglio Nazionale delle Ricerche, Napoli, Italy.
Pisanti
Simona
S
Malfitano
Anna Maria
AM
Bifulco
Maurizio
M
D000199:Actins / Q000378:metabolism; D000577:Amides / Q000494:pharmacology; D001095:Arachidonic Acids / Q000494:pharmacology*; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D002186:Cannabinoids / Q000494:pharmacology; D002462:Cell Membrane / Q000201:enzymology; D002465:Cell Movement / Q000187:drug effects*; D003599:Cytoskeleton / Q000378:metabolism; D003600:Cytosol / Q000201:enzymology; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D008798:Mevalonic Acid / Q000494:pharmacology; D009361:Neoplasm Invasiveness; D011725:Pyridines / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects*; D054460:rho-Associated Kinases / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
C443759:2-methylarachidonyl-2'-fluoroethylamide; D000199:Actins; D000577:Amides; D001095:Arachidonic Acids; D002186:Cannabinoids; D011725:Pyridines; C108830:Y 27632; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein; D008798:Mevalonic Acid