2-arachidonoylglycerol: a novel inhibitor of androgen-independent prostate cancer cell invasion.

Nithipatikom, Kasem; Endsley, Michael P; Isbell, Marilyn A; Falck, John R; Iwamoto, Yoshiki; Hillard, Cecilia J; Campbell, William B · Cancer Res · 2004

basic_science · Level V

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Abstract

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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