2-arachidonoylglycerol: a novel inhibitor of androgen-independent prostate cancer cell invasion.
Endocannabinoids have been implicated in cancer. Increasing endogenous 2-arachidonoylglycerol (2-AG) by blocking its metabolism inhibits invasion of androgen-independent prostate cancer (PC-3 and DU-145) cells. Noladin ether (a stable 2-AG analog) and exogenous CB1 receptor agonists possess similar effects. Conversely, reducing endogenous 2-AG by inhibiting its synthesis or blocking its binding to CB1 receptors with antagonists increases the cell invasion. 2-AG and noladin ether decrease protein kinase A activity in these cells, indicating coupling of the CB1 receptor to downstream effectors. The results suggest that cellular 2-AG, acting through the CB1 receptor, is an endogenous inhibitor of invasive prostate cancer cells.
Nithipatikom
Kasem
K
Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA. kasemn@mcw.edu
Endsley
Michael P
MP
Isbell
Marilyn A
MA
Falck
John R
JR
Iwamoto
Yoshiki
Y
Hillard
Cecilia J
CJ
Campbell
William B
WB
D000728:Androgens / Q000502:physiology; D001095:Arachidonic Acids / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D045744:Cell Line, Tumor; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D003512:Cyclohexanones / Q000494:pharmacology; D063388:Endocannabinoids; D005989:Glycerides / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D006868:Hydrolysis; D008071:Lipoprotein Lipase / Q000037:antagonists & inhibitors; D008297:Male; D009361:Neoplasm Invasiveness; D009376:Neoplasms, Hormone-Dependent / Q000378:metabolism / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000502:physiology
D000728:Androgens; D001095:Arachidonic Acids; D003512:Cyclohexanones; D063388:Endocannabinoids; D005989:Glycerides; D043884:Receptor, Cannabinoid, CB1; C036535:1,6-bis(cyclohexyloximinocarbonyl)hexane; C094503:glyceryl 2-arachidonate; C005953:monoolein; D017868:Cyclic AMP-Dependent Protein Kinases; D008071:Lipoprotein Lipase