RT Journal Article
SR Electronic
T1 Induction of Apoptosis by Cannabinoids in Prostate and Colon Cancer Cells Is Phosphatase Dependent
JF Anticancer Research
JO Anticancer Res
FD International Institute of Anticancer Research
SP 3799
OP 3807
VO 31
IS 11
A1 SANDEEP SREEVALSAN
A1 SONIA JOSEPH
A1 INDIRA JUTOORU
A1 GAYATHRI CHADALAPAKA
A1 STEPHEN H. SAFE
YR 2011
UL http://ar.iiarjournals.org/content/31/11/3799.abstract
AB 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.