Abstract
Aim:
We hypothesized that the anticancer activity of cannabinoids was linked to induction of phosphatases.
Materials and methods:
The effects of cannabidiol (CBD) and the synthetic cannabinoid WIN-55,212 (WIN) on LNCaP (prostate) and SW480 (colon) cancer cell proliferation were determined by cell counting; apoptosis was determined by cleavage of poly(ADP)ribose polymerase (PARP) and caspase-3 (Western blots); and phosphatase mRNAs were determined by real-time PCR. The role of phosphatases and cannabinoid receptors in mediating CBD- and WIN-induced apoptosis was determined by inhibition and receptor knockdown.
Results:
CBD and WIN inhibited LNCaP and SW480 cell growth and induced mRNA expression of several phosphatases, and the phosphatase inhibitor sodium orthovanadate significantly inhibited cannabinoid-induced PARP cleavage in both cell lines, whereas only CBD-induced apoptosis was CB1 and CB2 receptor-dependent.
Conclusion:
Cannabinoid receptor agonists induce phosphatases and phosphatase-dependent apoptosis in cancer cell lines; however, the role of the CB receptor in mediating this response is ligand-dependent.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Apoptosis / drug effects*
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Apoptosis / physiology
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Benzoxazines / pharmacology*
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Blotting, Western
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Calcium Channel Blockers / pharmacology
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Cannabidiol / pharmacology*
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Caspase 3 / metabolism
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Cell Line, Tumor
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Cell Proliferation
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Colonic Neoplasms / drug therapy*
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Colonic Neoplasms / enzymology
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Colonic Neoplasms / pathology*
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Humans
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Male
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Morpholines / pharmacology*
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Naphthalenes / pharmacology*
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Phosphoric Monoester Hydrolases / genetics
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Phosphoric Monoester Hydrolases / metabolism
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Poly(ADP-ribose) Polymerases / metabolism
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Prostatic Neoplasms / drug therapy*
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Prostatic Neoplasms / enzymology
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Prostatic Neoplasms / pathology*
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RNA, Messenger / genetics
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RNA, Small Interfering / genetics
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Real-Time Polymerase Chain Reaction
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Receptor, Cannabinoid, CB1 / antagonists & inhibitors
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Receptor, Cannabinoid, CB1 / genetics
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Receptor, Cannabinoid, CB1 / metabolism
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Receptor, Cannabinoid, CB2 / antagonists & inhibitors
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Receptor, Cannabinoid, CB2 / genetics
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Receptor, Cannabinoid, CB2 / metabolism
Substances
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Benzoxazines
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Calcium Channel Blockers
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Morpholines
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Naphthalenes
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RNA, Messenger
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RNA, Small Interfering
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Receptor, Cannabinoid, CB1
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Receptor, Cannabinoid, CB2
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Cannabidiol
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(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone
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Poly(ADP-ribose) Polymerases
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Phosphoric Monoester Hydrolases
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Caspase 3