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.
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 cannabinoidWIN-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.
Authors: Ahmed Lawan; Sameer Al-Harthi; Laurence Cadalbert; Anthony G McCluskey; Muhannad Shweash; Gianluca Grassia; Anne Grant; Marie Boyd; Susan Currie; Robin Plevin Journal: J Biol Chem Date: 2011-02-11 Impact factor: 5.157
Authors: Eva Eljaschewitsch; Anke Witting; Christian Mawrin; Thomas Lee; Peter M Schmidt; Susanne Wolf; Heide Hoertnagl; Cedric S Raine; Regine Schneider-Stock; Robert Nitsch; Oliver Ullrich Journal: Neuron Date: 2006-01-05 Impact factor: 17.173
Authors: Julia Kargl; Johannes Haybaeck; Angela Stančić; Liisa Andersen; Gunther Marsche; Akos Heinemann; Rudolf Schicho Journal: J Mol Med (Berl) Date: 2012-09-11 Impact factor: 4.599