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
- Research Support, N.I.H., Extramural
- Research Support, Non-U.S. Gov't
MeSH terms
- Apoptosis / drug effects*
- Apoptosis / physiology
- Benzoxazines / pharmacology*
- Blotting, Western
- Calcium Channel Blockers / pharmacology
- Cannabidiol / pharmacology*
- Caspase 3 / metabolism
- Cell Line, Tumor
- Cell Proliferation
- Colonic Neoplasms / drug therapy*
- Colonic Neoplasms / enzymology
- Colonic Neoplasms / pathology*
- Humans
- Male
- Morpholines / pharmacology*
- Naphthalenes / pharmacology*
- Phosphoric Monoester Hydrolases / genetics
- Phosphoric Monoester Hydrolases / metabolism
- Poly(ADP-ribose) Polymerases / metabolism
- Prostatic Neoplasms / drug therapy*
- Prostatic Neoplasms / enzymology
- Prostatic Neoplasms / pathology*
- RNA, Messenger / genetics
- RNA, Small Interfering / genetics
- Real-Time Polymerase Chain Reaction
- Receptor, Cannabinoid, CB1 / antagonists & inhibitors
- Receptor, Cannabinoid, CB1 / genetics
- Receptor, Cannabinoid, CB1 / metabolism
- Receptor, Cannabinoid, CB2 / antagonists & inhibitors
- Receptor, Cannabinoid, CB2 / genetics
- Receptor, Cannabinoid, CB2 / metabolism
Substances
- Benzoxazines
- Calcium Channel Blockers
- Morpholines
- Naphthalenes
- RNA, Messenger
- RNA, Small Interfering
- Receptor, Cannabinoid, CB1
- Receptor, Cannabinoid, CB2
- Cannabidiol
- (3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone
- Poly(ADP-ribose) Polymerases
- Phosphoric Monoester Hydrolases
- Caspase 3