Anticancer research · 2011
Induction of apoptosis by cannabinoids in prostate and colon cancer cells is phosphatase dependent.
СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Sreevalsan Sandeep, Joseph Sonia, Jutooru Indira, Chadalapaka Gayathri, Safe Stephen H
Аннотация
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.
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.
Предметные рубрики MeSH
ApoptosisBenzoxazinesBlotting, WesternCalcium Channel BlockersCannabidiolCaspase 3Cell Line, TumorCell ProliferationColonic NeoplasmsHumansMaleMorpholinesNaphthalenesPhosphoric Monoester HydrolasesPoly(ADP-ribose) PolymerasesProstatic NeoplasmsRNA, MessengerRNA, Small InterferingReal-Time Polymerase Chain ReactionReceptor, Cannabinoid, CB1Receptor, Cannabinoid, CB2