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[Cancer Research 64, 8826-8830, December 15, 2004]
© 2004 American Association for Cancer Research


Advances in Brief

2-Arachidonoylglycerol

A Novel Inhibitor of Androgen-Independent Prostate Cancer Cell Invasion

Kasem Nithipatikom1, Michael P. Endsley1, Marilyn A. Isbell1, John R. Falck3, Yoshiki Iwamoto2, Cecilia J. Hillard1 and William B. Campbell1

Departments of 1 Pharmacology and Toxicology and 2 Urology, Medical College of Wisconsin, Milwaukee, Wisconsin; and 3 Departments of Biochemistry and Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas

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.




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Copyright © 2004 by the American Association for Cancer Research.