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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Androgens / physiology
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Arachidonic Acids / antagonists & inhibitors
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Arachidonic Acids / biosynthesis
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Arachidonic Acids / metabolism
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Arachidonic Acids / physiology*
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Cell Line, Tumor
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Cyclic AMP-Dependent Protein Kinases / metabolism
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Cyclohexanones / pharmacology
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Endocannabinoids
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Glycerides / antagonists & inhibitors
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Glycerides / biosynthesis
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Glycerides / metabolism
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Glycerides / physiology*
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Humans
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Hydrolysis
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Lipoprotein Lipase / antagonists & inhibitors
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Male
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Neoplasm Invasiveness
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Neoplasms, Hormone-Dependent / metabolism
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Neoplasms, Hormone-Dependent / pathology*
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Prostatic Neoplasms / metabolism
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Prostatic Neoplasms / pathology*
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Receptor, Cannabinoid, CB1 / agonists
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Receptor, Cannabinoid, CB1 / antagonists & inhibitors
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Receptor, Cannabinoid, CB1 / biosynthesis
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Receptor, Cannabinoid, CB1 / physiology
Substances
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Androgens
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Arachidonic Acids
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Cyclohexanones
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Endocannabinoids
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Glycerides
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Receptor, Cannabinoid, CB1
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1,6-bis(cyclohexyloximinocarbonyl)hexane
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glyceryl 2-arachidonate
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monoolein
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Cyclic AMP-Dependent Protein Kinases
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Lipoprotein Lipase